Abstract: OBJECTIVE: In patients with soft tissue sarcoma (STS) the histological response (tumour grade regression: TGR) to neoadjuvant chemoradiotherapy (CRT) may influence the outcome. The main aim of the study was to evaluate the predictive value of 11C-methionine (MET) and 18F-FDG PET/CT in patients with STS treated with neoadjuvant CRT, correlating TGR with SUVmax (standardized uptake value) percentage variation before and after CRT. PATIENTS AND METHODS: Nine patients with STS already scheduled for a neoadjuvant CRT and surgery were enrolled. They underwent MET and FDG PET/CT in a one-day procedure before and after the CRT. Pre-therapy SUVmax and the percentage variation of SUVmax for MET and FDG were correlated with TGR according to the Huvos grade. Grades I-II were considered as partial responders (PR) and grades III-IV as complete responders (CR). RESULTS: FDG pre-treatment mean SUVmax in PR patients was 7.1, while in CR patients it was 13.2. Pre-treatment mean MET SUVmax in PR patients was 75, while in CR patients it was 4.9. The mean percentage variation in FDG SUVmax, was -21.2% in PR patients and -745% in CR patients while that for MET SUVmax was 48% in PR patients and -53.9% in CR patients. CONCLUSION: According to this preliminary study, the percentage variation in FDG before and after CRT seems to discriminate between PR and CR better than MET.

Abstract: PURPOSE: To evaluate the effect of the use of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in radiotherapy target delineation for head-and-neck cancer compared with CT alone. METHODS AND MATERIALS: A total of 38 consecutive patients with head-and-neck cancer were included in this study. The primary tumor sites were as follow: 20 oropharyngeal tumors, 4 laryngeal tumors, 2 hypopharyngeal tumors, 2 paranasal sinuses tumors, 9 nasopharyngeal tumors, and 1 parotid gland tumor. The FDG-PET and CT scans were performed with a dedicated PET/CT scanner in one session and then fused. Subsequently, patients underwent treatment planning CT with intravenous contrast enhancement. The radiation oncologist defined all gross tumor volumes (GTVs) using both the PET/CT and CT scans. RESULTS: In 35 (92%) of 38 cases, the CT-based GTVs were larger than the PET/CT-based GTVs. The average total GTV from the CT and PET/CT scans was 34.54 cm(3) (range, 3.56-109) and 29.38 cm(3) (range, 2.87-95.02), respectively (p < 0.05). Separate analyses of the difference between the CT- and PET/CT-based GTVs of the primary tumor compared with the GTVs of nodal disease were not statistically significant. The comparison between the PET/CT-based and CT-based boost planning target volumes did not show a statistically significant difference. All patients were alive at the end of the follow-up period (range, 3-38 months). CONCLUSION: GTVs, but not planning target volumes, were significantly changed by the implementation of combined PET/CT. Large multicenter studies are needed to ascertain whether combined PET/CT in target delineation can influence the main clinical outcomes.

Abstract: INTRODUCTION: The role of (18)F-FDG PET in the management of gynaecologic malignancies remains unclear mainly due to the failure of clinicians to appreciate the significance of this imaging tool. However, this under utilisation is being actively re-addressed with a large number of reviews and studies, particularly in the last few years. METHODS AND RESULTS: PET has been shown to have high sensitivity and specificity in the evaluation of relapse and nodal disease in cervical cancer, while other uses such as staging and monitoring response to therapies being under further investigation. Similarly, promising results have been published in the use of PET in patients affected by endometrial cancer and uterine sarcomas for detecting lymph nodes metastasis and recurrent disease. In ovarian cancer, PET appears to have a great potential in staging and assessment of disease relapse. An important utility of PET in gynaecologic tumours, which is shared with a large number of other malignancies, is its value in positively changing the patients' management. CONCLUSION: The surge in studies using PET in gynaecological malignancies is in its early stages, and further studies are required to optimise the role of PET in these conditions.

Abstract: The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

Abstract: PURPOSE: In lymphoma, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. However, there are no prospective studies investigating the value of serial FDG-PET over time in patients in complete remission. PATIENTS AND METHODS: All patients with lymphoma who achieved the first complete remission were prospectively enrolled onto the study and scheduled for serial FDG-PET scans at 6, 12, 18, and 24 months; further scans were then carried out on an annual basis. Overall, the population included 421 patients (160 patients with Hodgkin's lymphoma [HL], 183 patients with aggressive non-Hodgkin's lymphoma [NHL], and 78 patients with indolent follicular NHL). All patients had a regular follow-up evaluation, including complete clinical and laboratory evaluation, and final assessment of any suspect FDG-PET findings using other imaging procedures (computed tomography [CT] scan) and/or biopsy and/or clinical evolution. FDG-PET findings were reported as positive for relapse, inconclusive (when equivocal), or negative for relapse. RESULTS: PET enabled documentation of lymphoma relapse in 41 cases at 6 months, in 30 cases at 12 months, in 26 cases at 18 months, in 10 cases at 24 months, and in 11 cases at more than 36 months. All 36 patients with inconclusive positive PET underwent biopsy; only 12 (33%) of 36 patients had a concomitant suggestion of positivity on CT. A lymphoma relapse was diagnosed in 24 (66%) of 36 patients. CONCLUSION: Our results confirm FDG-PET as a valid tool for follow-up of patients with HL and NHL. In patients with inconclusive positive results, histologic confirmation plays an important role in identifying true relapse.

Abstract: BACKGROUND: Conventional imaging techniques [computed tomography (CT), ultrasound, magnetic resonance] and somatostatin receptor scintigraphy are often insufficient to make a conclusive diagnosis of bronchial carcinoid (BC). PET is commonly used for the assessment of lung cancer but 18F-fluorodeoxyglucose, the most frequently used PET tracer, presents a low sensitivity for the detection of neuroendocrine tumours (NETs). New PET radiopharmaceuticals such as 68Ga-DOTA peptides, which directly bind to somatostatin receptors and are usually expressed on NET cell surfaces, have been reported to be superior to both morphological and somatostatin receptor scintigraphy imaging for gastroenteropancreatic NETs. However, their role in BC has never been evaluated. Our aim is to evaluate the role of 68Ga-DOTA-NOC (68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide) PET for the assessment of BC patients. METHODS: Ten patients with pathologically proven well-differentiated BC and one patient with highly suggestive CT images for BC were studied by 68Ga-DOTA-NOC PET/CT. PET findings were compared with clinical follow-up, pathology and contrast-enhanced CT findings. RESULTS: 68Ga-DOTA-NOC PET/CT detected at least one lesion in nine of 11 patients and was negative in two. PET/CT and contrast-enhanced CT were discordant in eight of 11 patients, whereas in only three patients both provided similar results. PET/CT detected a higher number of lesions in five patients and excluded malignancy at sites considered positive on CT in three of 11; follow-up confirmed PET/CT findings in all patients. In PET/CT-positive patients, the mean maximal standardized uptake value was 25.9 [4.4-60.5]. On a clinical basis, PET/CT provided additional information in nine of 11 patients leading to the changes in the clinical management of three of nine patients. CONCLUSION: PET/CT with Ga-DOTA-NOC was useful in BC patients because it led to a better evaluation of the extent of the disease.

Abstract: The role of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the assessment of lymphoma patients is well established, and PET is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. The early evaluation of response to therapy (interim PET) has been reported to be an accurate predictor of progression-free survival, and end-treatment PET has been suggested to be unnecessary if interim PET results are negative. We report on a patient with Hodgkin's disease with a positive PET scan at presentation and a negative interim PET (carried out after three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine; ABVD). Despite uncomplicated clinical course, end-treatment PET (following six cycles) was positive, showing a very early relapse. For this reason, patient underwent further treatment; however, a complete remission was not obtained, and a poor prognosis is expected. This case testifies the possibility of early relapse of lymphoma even in the case of negative interim PET; it also supports the usefulness of end-treatment PET scan in lymphoma patients.

Abstract: The widespread use of several new non-cytotoxic drugs and the significant improvements in functional imaging highlights a number of difficulties in monitoring, interpreting and predicting treatment response in clinical practice. Certain guidelines for disease assessment after therapy are already available: the traditional Response Evaluation Criteria in Solid Tumours guidelines based on tumour size variations using conventional imaging technologies, the recent combined method developed by Choi and colleagues in gastrointestinal stromal tumour treated with tyrosine kinase inhibitors based on tumour density variations using computed tomography (CT), and the European Organization for Research and Treatment of Cancer criteria based on tumour glucose metabolism variations using fluorodeoxyglucose (FDG) positron emission tomography (PET). At the moment combined PET/CT response criteria are still not available. A number of new PET compounds other than FDG are also currently being developed to visualize specific cellular and molecular tumour pathways but their role in assessment and prediction of cancer treatment response has not yet been thoroughly investigated in a large series. However, in clinical practice many oncologists treat cancer patients with targeted therapies or chemotherapy and evaluate the response using conventional or functional imaging without appropriate and standardized guidelines. The aim of this study was to present a selection of clinical cases that illustrate the usefulness of new PET tracers and efficacy evaluation of new drugs. In the era of molecular imaging and molecular therapies, these cases highlight the urgency to develop new criteria for treatment assessment and the exigency of correctly interpreting the biological information obtained from new technologies, and introduce new concepts that require further investigation in clinical trials.

Abstract: (18)F-FDG PET value for the assessment of neuroendocrine tumours (NET) is limited. Preliminary studies indicate that somatostatin receptor PET using (68)Ga-DOTA-peptides is more accurate for disease assessment and provide additional data on receptor status, that are crucial for targeted radionuclide therapy. At present, however, few papers investigated the role of (68)Ga-DOTA-NOC PET in NET, especially in unusual situations. The purpose of the present study was to evaluate (68)Ga-DOTA-NOC for the evaluation of NET of uncommon presentation. Patients with biopsy-proven NET were scheduled for (68)Ga-DOTA-NOC PET; we excluded from further evaluation cases with most common NET tumours (gastro-entero-pancreatic and pulmonary localization of primary lesion, MEN syndromes, medullary thyroid carcinoma, pheochromocytomas). PET results were compared with findings of conventional imaging, including CT, ultrasonography, MR and somatostatin receptor scintigraphy; finally PET results were compared with follow-up data with respect to the impact on patient management. Fourteen patients were finally enrolled; primary tumours were located at uterine level (3 cases), prostate (3 cases), ovary (1 case), kidney (1 case), breast (1 case), ear (1 case); also 3 cases of paraganglioma (at neck, abdominal and mediastinum level) and 1 case of lymphoma were included. (68)Ga-DOTA-NOC PET was positive, showing at least 1 lesion, in 6/14 cases while 5 cases turned out negative and 2 inconclusive. On a clinical basis, (68)Ga-DOTA-NOC provided additional information in comparison to conventional imaging procedures in 7/14 cases, and was considered useful in 12/14 patients, with 8 patients in which (68)Ga-DOTA-NOC PET was determinant for patient's management. Although the number of patients studied is limited, our data show that (68)Ga-DOTA-NOC can be usefully applied for the evaluation of NET of uncommon presentation; in particular very promising results were obtained in paraganglioma. On the other hand, care has to be paid when studying lesions localized at sites of physiological concentration of the tracer, and in presence of inflammation.

Abstract: INTRODUCTION: After imatinib treatment, the surgical management of patients affected by gastrointestinal stromal tumor (GIST) has been widely reported and often considered by many oncologists in clinical practice. Surgical results are correlated with disease responsiveness to tyrosine kinase inhibitors and with complete extirpation of all tumor sites. By now, no report specifically addressing surgical management after second-line treatment with sunitinib is still available. Most patients have an unresectable disease and do not have any other therapeutical options except for clinical trials. MATERIALS AND METHODS: We report two clinical cases of patients with metastatic GISTs, who underwent surgery after sunitinib, and discuss the surgical management option in this clinical setting. RESULTS: Both our patients had a long, durable stable disease on sunitinib, but one developed a chronic mild bleeding that does not call for emergency surgical interventions and the other one developed chronic heart toxicity. They were proposed to undergo surgery despite the unresectable diseases and received an incomplete resection because of residual metastatic lesions. They restarted sunitinib after surgery. CONCLUSIONS: The poor prognosis after sunitinib treatment and the absence of alternative validated options open the debate on the assessment of surgical management of metastatic GISTs in this setting. The role of surgery should be investigated in clinical trials; however, the enrollment may be difficult. In clinical practice and after a multidisciplinary case patient discussion, surgery could represent a reasonable choice for advanced GISTs especially if the risk of surgery-related death is not too high.

Abstract: PURPOSE: (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. AIM: The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. MATERIALS AND METHODS: Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). RESULTS: The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. CONCLUSIONS: Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.

Abstract: BACKGROUND: Conventional imaging (CI) techniques are inadequate for lymph node (LN) staging in prostate cancer (PCa). OBJECTIVES: To assess the accuracy of (11)C-Choline positron emission tomography/computerized tomography (PET/CT) for LN staging in intermediate-risk and high-risk PCa and to compare it with two currently used nomograms. DESIGN, SETTING, AND PARTICIPANTS: From January 2007 to September 2007, 57 PCa patients at intermediate risk (n=27) or high risk (n=30) were enrolled at two academic centres. All patients underwent preoperative PET/CT and radical prostatectomy with extended pelvic LN dissection (PLND). Risk of LN metastasis (LNM) was assessed using available nomograms. MEASUREMENTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and number of correctly recognized cases for LNM detection at PET/CT were assessed. The accuracy of PET/CT for LNM detection was compared with the accuracy of nomograms for LNM prediction by using receiver operating characteristic (ROC) analysis. RESULTS AND LIMITATIONS: Fifteen patients (26%) had LNMs, and a total of 41 LNMs were identified. On a patient analysis, sensitivity, specificity, PPV, NPV, and number of correctly recognized cases at PET/CT were 60.0%, 97.6%, 90.0%, 87.2%, and 87.7% while, on node analysis, these numbers were 41.4%, 99.8%, 94.4%, 97.2%, and 97.1%. The mean diameter (in mm) of the metastatic deposit of true-positive LNs was significantly higher than that of false-negative LNs (9.2 vs 4.2; p=0.001). PET/CT showed higher specificity and accuracy than the nomograms; however, in pairwise comparison, the areas under the curve (AUCs) were not statistically different (all p values >0.05). CONCLUSIONS: In patients with intermediate-risk and high-risk PCa, (11)C-Choline PET/CT has quite a low sensitivity for LNM detection but performed better than clinical nomograms, with equal sensitivity and better specificity.

Abstract: PURPOSE: The aim of this study was to evaluate the clinical significance of positive axillary findings in patients with Hodgkin's disease and non-Hodgkin's lymphoma during follow-up with 18F-fluorodeoxyglucose-PET. MATERIALS AND METHODS: We retrospectively reviewed PET scans carried out in 543 patients during follow-up. Patients with reports describing any increased fluorodeoxyglucose uptake at the axillary level were selected (106 cases) and final assessment of the findings was available in 78 patients (17 Hodgkin's disease, 51 non-Hodgkin's lymphoma). PET scans were performed after standard procedure and reports were interpreted as positive or negative on the basis of visual analysis. At the moment of the scan all patients had no clinical or laboratory sign of relapse, and had not received therapy for at least 6 months. All PET results were compared with other diagnostic procedures (ultrasonography and computed tomography), biopsy and/or follow-up data. RESULTS: Of 78 patients, 24 were PET positive in one axilla, 23 had axillary findings and one or more other extra axillary sites, five patients were positive in both axillas and 26 were positive in both axillas and one or more other sites. Of the 24 patients with single axillary finding, the result for five was true positive and for 19 it was false positive. Sixteen cases of the 23 patients with PET positive at one axilla and other sites had a true positive result, whereas seven had a false positive result. Only one of five patients with both axillas being positive at PET turned out to be true positive; finally, 23 cases from the 26 patients with both axillas and other findings had a true positive result and three of 26 had a false positive result. Overall, 45 out of 78 patients were true positive and 33 were false positive. CONCLUSION: Axillary findings are relatively frequent and can be isolated or in association with other findings. In patients with axillary involvement only the frequency of false positivity results is elevated and therefore these cases need to be evaluated carefully. In contrast, axillary findings associated with other pathological localizations show true positive results in most cases, thus indicating a high likelihood of disease recurrence. Standardized uptake values showed a limited role for discriminating true-positive and false-positive findings.

Abstract: This study reports on our experience with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in pediatric patients affected by Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). We studied 20 pediatric subjects (12 males, 8 females; mean age, 10 years; range, 6 months to 14 years) with malignant lymphoma (9 HD, 11 NHL) for a 4-year period of time. Overall, 45 PET scans were performed: 7 at disease presentation and 38 for evaluation of response to therapy or follow-up study. All PET results were compared with conventional imaging (CI), mainly computed tomography (CT) and/or magnetic resonance imaging (MRI), and supported by clinical follow-up and/or histologic data. In 18 of 20 patients, PET findings correctly identified the status of disease. Two (2) subjects (respectively, 1 HD and 1 NHL, both at follow-up) resulted falsely positive: 1 due to prominent thymic uptake, and the other due to nonspecific inflammation. Of 45 scans, PET findings were consistent with clinical follow-up and other CI data in 43 cases (16 true-positive and 27 true-negative results) and resulted falsely positive in the remaining 2 scans. On a lesion-by-lesion basis (overall, 153 lesions: 84 nodal and 69 extranodal), we found a concordance between CI and PET findings in 25 nodal (29.8%) and in 22 extranodal sites (32%). PET was more accurate than CI, as it identified active disease in 1 patient negative at CI and excluded relapse in 6 patients with inconclusive CI and in 2 patients with a falsely positive CI. Overall, PET sensitivity and specificity was 100% and 93% versus 94% sensitivity and 72.4% specificity for CI. This comparative study shows FDG PET to be more accurate than CI in evaluating children with lymphoma. Our data also confirms that 18 F-FDG PET may show false-positive findings.

Abstract: With increasing application of positron-emission tomography (PET) imaging, familiarity with the applications of PET in genitourinary oncology, especially prostate-cancer (PCa) imaging, becomes important. PET studies provide functional information using radiolabeled tracers, with fluoro-dexoxy-glucose (FDG) being the most commonly used. Nevertheless FDG has limitations for evaluation of PCa patients and therefore alternative tracers are being investigated. To date, the best results have been obtained with 11C-choline and 11C-acetate PET, which seem to demonstrate similar values in this field. We review the current role of PET in PCa patients based on data published in the literature as well as our own experience. Most studies of PET imaging of PCa address three goals: a) detecting primary PCa; b) staging PCa; and c) assessing PCa recurrence. From available results, routine clinical use of 11C-choline PET cannot be recommended for detecting and staging primary PCa. At present, the only clinical indication for imaging PCa with 11C-choline-PET is evaluation of suspected recurrence after treatment.

Abstract: BACKGROUND: A prospective, single-arm, open-label, nonrandomized phase II combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus radioimmunotherapy trial was conducted to evaluate the efficacy and safety in untreated elderly diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS: From February 2005 to April 2006, in our institute we treated 20 eligible elderly (age > or =60 years) patients with previously untreated DLBCL using a novel regimen consisting of six cycles of CHOP chemotherapy followed 6-10 weeks later by (90)Y ibritumomab tiuxetan. RESULTS: The overall response rate to the entire treatment regimen was 100%, including 95% complete remission (CR) and 5% partial remission. Four (80%) of the five patients who achieved less than a CR with CHOP improved their remission status after radioimmunotherapy. With a median follow-up of 15 months, the 2-year progression-free survival was estimated to be 75%, with a 2-year overall survival of 95%. The (90)Y ibritumomab tiuxetan toxicity included grade > or =3 hematologic toxicity in 12 of 20 patients; the most common grade > or =3 toxic effects were neutropenia (12 patients) and thrombocytopenia (7 patients). Transfusions of red blood cells and/or platelets were given to one patient. CONCLUSION: This study has established the feasibility, tolerability, and efficacy of this regimen for elderly patients with DLBCL.

Abstract: AIM: To evaluate the value of 18F-fluorodeoxy-glucose (FDG) positron emission tomography with computed tomography (PET/CT) in myeloma in patients presenting with a solitary plasmacytoma of bone (SPB). PATIENTS AND METHODS: Fourteen consecutive patients studied since 2006, all having a diagnosis of SPB before PET/CT imaging took part in this study. In 3 patients PET/CT was performed for staging while in the remaining 11 it was used to monitor therapy. PET/CT was performed using a dedicated tomograph 60-90 minutes after intravenous injection of 53 MBq/kg of 18F-FDG and the results were compared to other diagnostic procedures [radiographs and magnetic resonance imaging (MRI)], biopsy, and other available follow-up data. RESULTS: In 8/14 patients, PET/CT scans showed previously unsuspected sites of increased FDG accumulation. In 6/8 patients, FDG uptake was considered pathologic, depicting myeloma involvement in bone, while in the remaining cases, findings were considered incidental and not related to myeloma. PET findings attributed to myeloma were confirmed (i.e. true positives) in 6/6 cases (100%) and in all patients with findings reported as non-pathologic, myeloma was excluded (100% true negatives). CONCLUSION: Our preliminary data in a small number of cases suggests that there are a group of patients with SPB (local disease) in whom FDG PET/CT may detect other unsuspected sites of bone involvement, upstaging the extent of the disease. In these cases, SPB may be a local manifestation of multiple myeloma where other sites of involvement have eluded detection by other less sensitive imaging modalities (i.e. skeletal surveys) or anatomically restricted imaging (i.e., less than total body MR or CT). Finding other sites of involvement have significant implications for appropriate treatment of myeloma.

Abstract: BACKGROUND: Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. AIM: As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. METHODS: Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. RESULTS: Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). CONCLUSION: According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

Abstract: BACKGROUND AND OBJECTIVES: Bone lesions in multiple myeloma (MM) have been traditionally detected by whole body X-ray (WBXR) survey although magnetic resonance imaging (MRI) has become the gold standard for detecting MM involvement of the spine and pelvis. The aim of this study was to compare a new technique, positron emission tomography (PET) with 18F fluorodeoxyglucose (FDG) integrated with computed tomography (18F-FDG PET-CT), with MRI and WBXR for baseline assessment of bone disease in MM. DESIGN AND METHODS: We prospectively compared 18F-FDG PET-CT, MRI of the spine-pelvis and WBXR in a series of 46 patients with newly diagnosed MM. In 23 patients who received up front autologous transplantation, we also compared post-treatment PET-CT scans with MR images of the spine and pelvis. RESULTS: Overall, PET-CT was superior to planar radiographs in 46% of patients, including 19% with negative WBXR. In 30% of patients, PET-CT scans of the spine and pelvis failed to show abnormal findings in areas in which MRI revealed an abnormal pattern of bone marrow involvement, more frequently of diffuse type. In contrast, in 35% of patients PET-CT enabled the detection of myelomatous lesions in areas which were out of the field of view of MRI. By combining MRI of the spine- pelvis and 18F-FDG PET-CT, the ability to detect sites of active MM, both medullary and extramedullary, was as high as 92%. Following transplantation, 15 patients had negative PET-CT scans (including 13 with a very good partial response or at least a near complete response), but only 8 had normal MRI. INTERPRETATION AND CONCLUSIONS: MRI of the spine and pelvis still remains the gold standard imaging technique for the detection of bone marrow involvement in MM. 18F-FDG PET-CT provides additional and valuable information for the assessment of myeloma bone disease in areas not covered by MRI.

Abstract: PURPOSE: The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2-3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time. METHODS: We studied 23 nude mice, in which 7 x 10(6) rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases. RESULTS: The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals) while the negative predictive value was 46% (6/13 animals). In the whole group of animals, mean TBR increased scan by scan. There was a statistically significant difference in TBR between 2 and 20 days after inoculation. Necrosis was present at the second scan in two animals, at the third scan in six animals and at the fourth scan in 11 animals. CONCLUSION: The high positive predictive value of FDG PET 2 days after inoculation means that an animal with a first positive scan has a very high likelihood of developing a mass and can be treated at an early stage with an experimental drug. Animals negative at this point in time will never develop a mass or will eventually do so at a late phase. As 2 of the 16 (12.5%) positive animals had necrosis at the second scan, indicating a vascular mismatch, it may be argued that animals should be treated 2 days after inoculation to guarantee homogeneous vascularisation (thereby ensuring a good drug supply within the tumour) in all subjects.

Abstract:

Abstract: PURPOSE: The purpose of this study was to evaluate the reliability of positron emission tomography (PET) in patients with follicular lymphoma (FL) after induction treatment. PATIENTS AND METHODS: In all, 45 previously untreated patients with FL were studied with PET and computed tomography (CT) scans after chemotherapy induction treatment (fludarabine-containing regimens and CHOP [cyclophosphamide/doxorubicin/vincristine/prednisone] chemotherapy). Histopathologic analysis was performed when considered necessary. RESULTS: After treatment, 4 of 5 patients (80%) who had CT-negative/PET-positive findings experienced relapse/progression, compared with only 1 of 22 patients (4.5%) in the CT-negative/PET-negative subset. Among the 18 patients with CT-positive findings, all 6 patients (100%) who had PET-positive findings experienced relapse or progression, compared with 1 of 12 patients (8.3%) who had PET-negative findings. The 2-year progression-free survival rates were 20% and 90% in the CT-negative/PET-positive and CT-positive/PET-negative subsets, respectively (P = 0.0031). During the follow-up, 2 patients, who presented a PET positivity with a negative CT scan, underwent a lymph node biopsy, which confirmed the presence of FL infiltration. CONCLUSION: In patients with FL, persisting PET positivity is predictive of early disease progression, because it is still highly likely that patients with PET-negative findings will ultimately progress, but this has not yet been manifested during the period of observation.

Abstract: PURPOSE: To assess whether 18F-dopa PET/CT is able to provide information relevant in changing the clinical management of patients with gastro-enteropancreatic (GEP) tumours where there is negative or inconclusive conventional radiological imaging (ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) and 111In-pentetreotide scintigraphy. MATERIALS AND METHODS: From January 2005 to October 2006, 84 patients with clinical and biochemical suspicion of GEP tumours were investigated by US and CT scans, MRI and 111In-pentetreotide scintigraphy. In 13/84 (15.4%) both conventional radiological imaging and 111In-pentetreotide scintigraphy provided negative or inconclusive findings, and patients were referred for 18F-dopa PET/CT imaging. Each patient received 5.3 MBq x kg(-1) 18F-dopa intravenously, and imaged 60 min later using a hybrid PET/CT scanner. RESULTS: 18F-dopa PET/CT detected the primary tumour in all 13 patients (size range, 7-26 mm, mean, 18 mm; SUVmax range, 2.3-16.3, mean, 5.7) and further 12 unsuspected lesions (size range, 12-23 mm, mean 17; SUVmax range 2.8-12.7, mean 4.6). Confirmation of the PET/CT findings was obtained in all patients from histopathological analysis of tissue obtained after surgery and/or biopsy. All the 18F-dopa-positive primary lesions were confirmed as being the primary tumour at histology, whereas of the other 12 unsuspected 18F-dopa-positive lesions, 11 were found to be metastatic deposits and one due to unspecific inflammation (one false positive result). Notably, the results of 18F-dopa PET/CT imaging changed the clinical management in 11/13 patients (84%). CONCLUSIONS: Our preliminary results suggest that 18F-dopa PET/CT has a promising role in GEP patients with negative or inconclusive findings at conventional radiological imaging and 111In-pentetreotide scintigraphy. The findings were helpful in biopsy guidance and played a major role in changing the management of those patients.

Abstract: BACKGROUND AND OBJECTIVES: Follow-ups of patients with mediastinal lymphoma are not accurate if they rely on computed tomography (CT). Positron emission tomography (PET) has been suggested to be useful in several lymphoma settings, such as initial staging, evaluation of residual masses after therapy, and assessment of response early in the course of treatment. The aim of this retrospective study was to verify the reliability of positive PET scans of the mediastinum in following up patients with mediastinal lymphoma, using histological findings as a comparison. DESIGN AND METHODS: From January 2002 to July 2005, 151 patients with mediastinal lymphoma (57 with Hodgkin's disease [HD] and 94 with aggressive non-Hodgkin's lymphoma [NHL]) were followed-up after the end of front-line treatment. Patients with a positive PET scan of the mediastinum underwent CT scanning and surgical biopsy. RESULTS: In 30 (21 HD and 9 NHL) out of 151 patients (20%) a suspicion of lymphoma relapse was raised based on positive mediastinal PET scanning. Histology confirmed this suspicion in 17 (10 HD and 7 NHL) out of 30 patients (57%), whereas either benign (9 fibrosis, 3 sarcoid-like granulomatosis) or unrelated neoplastic conditions (1 thymoma) were demonstrated in the remaining 13 patients (43%). SUVmax was significantly higher among patients who had signs of relapse (17 true positive cases) than among those who stayed in remission (13 false positive cases), the median values being 5.95 (range, 3.5-26.9) and 2.90 (range, 1.4-3.3), respectively (p=0.01). INTERPRETATION AND CONCLUSIONS: We suggest that a positive PET scan of the mediastinum of a patient being followed-up for a mediastinal lymphoma should not be considered sufficient for diagnostic purposes in view of its lack of discrimination. Histological confirmation can safely be carried out with various biopsy techniques, the choice of which should be made on the basis of the findings of the clinical and imaging studies of the individual case.

Abstract: AIMS: To (a) assess the accuracy of 18F-FDG PET/CT in distinguishing malignant from benign pelvic lesions, compared to transvaginal ultrasonography (TVUS) and (b) to establish the role of whole-body 18F-FDG PET/CT, compared to contrast enhanced computed tomography (CT), in staging patients with ovarian cancer. PATIENTS: Fifty consecutive patients with a pelvic lesion, already scheduled for surgery on the basis of physical examination, TVUS, and serum Ca125 levels, were enrolled in the study. Patients' age ranged between 23 and 89 years (mean 64). All patients underwent TVUS including a colour Doppler study followed by a thorax and abdominal CT scan, and whole-body 18F-FDG PET/CT within 2 weeks prior to surgery. Histological findings obtained at surgery were taken as the 'gold standard' to compare 18F-FDG PET/CT and TVUS, and 18F-FDG PET/CT vs. CT. When tissue analysis showed ovarian cancer, the accuracy of 18F-FDG PET/CT and CT were compared for the purpose of obtaining a precise staging. RESULTS: At surgery, the ovarian lesions were malignant in 32/50 patients (64%) and benign in the remaining 18/50 patients (36%). The sensitivity, specificity, NPV, PPV and accuracy of 18F-FDG PET/CT were 87%, 100%, 81%, 100% and 92%, respectively, compared with 90%, 61%, 78%, 80% and 80%, respectively, for TVUS. In staging ovarian cancer, 18F-FDG PET/CT results were concordant with final pathological staging in 22/32 (69%) patients while CT results were concordant in 17/32 (53%) patients. CT incorrectly down-staged four out of six stage IV patients by missing distant metastasis in the liver, pleura, mediastinum, and in left supraclavicular lymph nodes, which were correctly detected by 18F-FDG PET/CT. CONCLUSION: PET/CT with 18F-FDG provides additional value to TVUS for the differential diagnosis of benign from malignant pelvic lesions, and to CT for the staging of ovarian cancer patients.

Abstract: BACKGROUND: The aim of the study was to evaluate whether the therapy-induced reduction of the (18)F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) maximum standardized uptake value in patients with advanced gastric adenocarcinoma treated with chemotherapy plus cetuximab could predict the objective response and outcome early during the treatment. METHODS: The study was performed as a part of a phase II trial evaluating cetuximab plus the leucovorin/5-fluorouracil/irinotecan (FOLFIRI) regimen. The objective response was evaluated according to the response evaluation criteria in solid tumors (RECIST) every 6 weeks. The early metabolic response evaluated by 18F-FDG-PET was assessed according to our own evaluated cutoff value (<35%) after receiver operating characteristic (ROC) analysis. RESULTS: Twenty of 22 patients had positive baseline 18F-FDG-PET. The best RECIST response was: complete response (CR), 3; partial response (PR), 9; stable disease (SD), 8. Twelve patients (60%) were classified as metabolic responders and 8 (40%) as nonresponders. At the median follow-up time of 11 months, median time to disease progression (TTP) and overall survival (OS) for early metabolic responders versus nonresponders were 11 versus 5 months (P = 0.0016) and 16 versus 6 months (P = 0.1493), respectively. CONCLUSION: The early metabolic response evaluated by 18F-FDG-PET predicted the clinical outcome in this series of patients with advanced gastric cancer treated with chemotherapy plus cetuximab.

Abstract: Around 20-30% of patients with hepatic metastasis from colorectal cancer can undergo liver resection, but the increased response rate obtained with the addition of monoclonal antibodies to chemotherapy regimens could result in a higher rate of liver surgery. In this report we describe the case of a patient who underwent a liver resection after neoadjuvant treatment with capecitabine, oxaliplatin and bevacizumab and who achieved a complete pathological response of the liver metastasis. A preoperative CT scan demonstrated a partial response to the treatment while 18FDG-PET scan correctly evaluated the complete pathological response in the liver and detected an active interaortocaval lymph node metastasis. New specific studies are required to evaluate the imaging response in metastatic colorectal cancer patients especially after treatment with new, targeted agents.

Abstract: PURPOSE: To retrospectively compare sensitivity and specificity of magnetic resonance (MR) imaging, three-dimensional (3D) MR spectroscopy, combined MR imaging and 3D MR spectroscopy, and carbon 11 (11C)-choline positron emission tomography (PET)/computed tomography (CT) for intraprostatic tumor sextant localization, with histologic findings as reference standard. MATERIALS AND METHODS: The local ethics committee on human research provided approval and a waiver of informed consent for the retrospective study. MR imaging, 3D MR spectroscopy, and 11C-choline PET/CT results were retrospectively reviewed in 26 men with biopsy-proved prostate cancer (mean age, 64 years; range, 51-75 years) who underwent radical prostatectomy. Cancer was identified as areas of nodular low signal intensity on T2-weighted MR images. At 3D MR spectroscopy, choline-plus-creatine-to-citrate and choline-to-creatine ratios were used to distinguish healthy from malignant voxels. At PET/CT, focal uptake was visually assessed, and maximum standardized uptake values (SUVs) were recorded. Agreement between 3D MR spectroscopic and PET/CT results was calculated, and ability of maximum SUV to help localize cancer was assessed with receiver operating characteristic analysis. Significant differences between positive and negative sextants with respect to mean maximum SUV were calculated with a paired t test. RESULTS: Sensitivity, specificity, and accuracy were, respectively, 55%, 86%, and 67% at PET/CT; 54%, 75%, and 61% at MR imaging; and 81%, 67%, and 76% at 3D MR spectroscopy. The highest sensitivity was obtained when either 3D MR spectroscopic or MR imaging results were positive (88%) at the expense of specificity (53%), while the highest specificity was obtained when results with both techniques were positive (90%) at the expense of sensitivity (48%). Concordance between 3D MR spectroscopic and PET/CT findings was slight (kappa=0.139). CONCLUSION: In localizing cancer within the prostate, comparable specificity was obtained with either 3D MR spectroscopy and MR imaging or PET/CT; however, PET/CT had lower sensitivity relative to 3D MR spectroscopy alone or combined with MR imaging.

Abstract: BACKGROUND: The aim of the study was to evaluate the usefulness of 18F-FDG-PET in patients with gastric lymphoma, in particular those affected by mucosa-associated lymphoid tissue (MALT) type and aggressive gastric non-Hodgkin's lymphoma (NHL). MATERIAL AND METHODS: The study group consists of 15 patients with a previous diagnosis of gastric NHL referred to our PET centres in Bologna Hospital and Rovigo Hospital, Italy, in the period 2003-2004. In 9/15 patients the subsequent histological evaluation was consistent with a gastric MALT lymphoma, while aggressive gastric NHL was diagnosed in the other 6/15. PET scan was carried out in patients with known active disease in order to stage or re-stage disease prior to treatment or in patients in complete clinical remission to monitor disease during follow up. Patients were considered in complete clinical remission if free from disease for at least 8 months after chemotherapy or surgery.18F-FDG PET was performed following standard procedures. RESULTS: Overall 18F-FDG-PET was true positive in all cases of gastric MALT and non-MALT aggressive NHL with known active disease, while no pathological 18F-FDG uptake was evident in the subjects who were in complete clinical remission. The degree of 18F-FDG uptake (mean SUVmax values) in MALT lymphoma was much less intense in comparison to aggressive gastric NHL, suggesting a prognostic role of SUV calculation in gastric lymphomas. CONCLUSION: Our data demonstrate the significant accuracy of 18F-FDG-PET in detecting active disease in gastric lymphoma of both MALT and non-MALT NHL type. A higher SUV value appears to be related to a more aggressive disease.

Abstract: In recent years a number of studies have been published showing strong value of positron emission tomography using 18-Fluorine 2-fluoro-deoxy-D-glucose (FDG-PET) in term of diagnosis, response to treatment, disease recurrence and prognostic indicator in early restaging. This study observed 17 patients who presented contemporary disease progression in some localizations as well as regression in others (PROG + REG pattern); this investigation assessed that this unusual pattern of FDG uptake lead to an unfavorable prognosis. Among 1280 FDG-PET scans performed between August 2003 and December 2004 on patients affected by lymphoma with suspected recurrence, attention was focused on 17 patients presenting a PROG + REG pattern. At follow-up (4 months) only 1/17 (6%) patient was in complete remission after salvage therapy, while 6/17 (35%) had stable disease and 10/17 (59%) had rapid progression of the disease. This study further strengthens the role of FDG-PET in lymphoma patients follow-up, as it can provide useful information to better differentiate those cases who may benefit from conventional treatments from others in whom additional treatment would provide avoidable toxicity.

Abstract: BACKGROUND: It is important to distinguish between responders to standard treatment and non-responders Hodgkin's disease (HD) patients. PATIENTS AND METHODS: Between June 2003-September 2004, in our institute, 40 newly-diagnosed patients with advanced stage HD were consecutively treated with ABVD chemotherapy for six cycles. All these patients underwent staging/restaging: computed tomography (CT) and positron emission tomography (PET) at time 0, PET after two cycles, CT and PET after four and six cycles. RESULTS: After two cycles (PET-2), the PET was negative in 28/40 (70%), positive in 8/40 (20%), and minimal residual uptake (MRU) was present in the remaining four (10%) patients. After treatment, among eight patients who were PET-2+, seven showed refractory disease and one had relapse after 3 months. All four patients with MRU at the PET-2 became PET- during the further four cycles and, after treatment, three were in complete response (CR) and one relapsed after 5 months. All 28 PET negative patients at the PET-2 remained PET negative and all of them were in CR after treatment. CONCLUSIONS: The PET use for early (after two cycles) response assessment in HD patients is a significant step forward and has the potential to help physicians make crucial decisions about further treatment.

Abstract: PURPOSE: Multiple myeloma (MM) is a malignant B cell and plasma cell disorder which involves the skeleton in more than 80% of patients at diagnosis. The aim of this study was to compare whole-body X-ray (WBXR), MRI and (18)F-FDG PET/CT in patients with MM. METHODS: The study population comprised 28 newly diagnosed MM patients. Findings of (18)F-FDG PET/CT were compared with those of WBXR and MRI with regard to the number and site of lesions detected. RESULTS: Comparing (18)F-FDG PET/CT and WBXR, it was found that in 16/28 pts (57%) (18)F-FDG PET/CT detected more lesions, all of which were located in the skeleton. Nine of these 16 patients had a completely negative WBXR survey. In 12/28 pts (43%) the two methods yielded equivalent findings. Comparing (18)F-FDG PET/CT and MRI, it was found that in 7/28 pts (25%), (18)F-FDG PET/CT detected more lytic bone lesions, all of which were located outside the field of view of MRI (bone lesions in six cases and a soft tissue lesion in one). In 14/28 pts (50%), (18)F-FDG PET/CT and MRI detected the same number of lesions in the spine and pelvis, while in 7/28 pts (25%) MRI detected an infiltrative pattern in the spine whereas (18)F-FDG PET/CT was negative. CONCLUSION: (18)F-FDG PET/CT appears to be more sensitive than WBXR for the detection of small lytic bone lesions, whereas it has the same sensitivity as MRI in detecting bone disease of the spine and pelvis. On the other hand, MRI may be superior to (18)F-FDG PET/CT in diagnosing an infiltrative pattern in the spine. Therefore, careful evaluation of MM bone disease at diagnosis should include both MRI of the spine and (18)F-FDG PET/CT.

Abstract: PURPOSE: Scintigraphic localisation of parathyroid glands is often unsuccessful in patients with renal failure on chronic haemodialysis who have secondary hyperparathyroidism (HPT). The purpose of this study was to investigate the use of (11)C-methionine PET/CT to detect hyperfunctioning parathyroid glands in patients with renal failure on chronic haemodialysis who had (99m)Tc-sestamibi-negative HPT. METHODS: (11)C-methionine PET/CT was performed in 18 patients (11 women and 7 men, aged 42-79 years; mean age 57.8 years) on haemodialysis for renal failure (2-14 years' duration), with normo-, hypo- or hypercalcaemia and HPT not localised by either dual-tracer (99m)Tc-pertechnetate/(99m)Tc-sestamibi subtraction scans or dual-phase (99m)Tc-sestamibi scans. RESULTS: In three of ten patients with normo- or hypocalcaemic HPT there was increased (11)C-methionine accumulation in one gland. Seven of eight patients with hypercalcaemic HPT showed increased uptake: in five of these patients increased (11)C-methionine accumulation was present in one gland, while in two it was demonstrated in two glands. All patients also had high-resolution ultrasound of the neck and were treated with subtotal parathyroidectomy, leaving a remnant of the smallest of the four glands. Regardless of their size, all glands with abnormal (11)C-methionine parathyroid uptake were removed, and all demonstrated parathyroid hyperplasia. All patients developed post-parathyroidectomy hypoparathyroidism and one patient with normocalcaemic HPT relapsed 8 months after surgery. CONCLUSION: These data suggest that (11)C-methionine PET/CT may be used to identify hyperfunctioning parathyroid glands in non-primary HPT, and especially hypercalcaemic HPT, when conventional (99m)Tc-sestamibi imaging is non-localising.

Abstract: PURPOSE: (11)C-choline positron emission tomography is an innovative imaging technique for prostate cancer. We assessed the sensitivity of positron emission tomography used together with computerized tomography for intraprostatic localization of primary prostate cancer on a nodule-by-nodule basis, and compared its performance with 12-core transrectal biopsy. MATERIALS AND METHODS: In 43 patients with known prostate cancer who had received positron emission tomography/computerized tomography before initial biopsy, we assessed sensitivity of positron emission tomography/computerized tomography for localization of nodules 5 mm or greater (those theoretically large enough for visualization) using radical prostatectomy histopathology as the reference standard. Comparison with transrectal ultrasound guided biopsy was based on sextant assessment of all cancer foci following sextant-by-sextant matching and reconstruction. Sensitivity/specificity of positron emission tomography/computerized tomography and magnetic resonance imaging for prediction of extraprostatic extension was also assessed. RESULTS: Positron emission tomography/computerized tomography showed 83% sensitivity for localization of nodules 5 mm or greater. At logistic regression analysis only nodule size appeared to influence sensitivity. At sextant assessment positron emission tomography/computerized tomography had slightly better sensitivity than transrectal ultrasound guided biopsy (66% vs 61%, p = 0.434) but was less specific (84% vs 97%, p = 0.008). For assessment of extraprostatic extension, sensitivity of PET/CT was low in comparison with magnetic resonance imaging (22% vs 63%, p <0.001). CONCLUSIONS: Positron emission tomography/computerized tomography has good sensitivity for intraprostatic localization of primary prostate cancer nodules 5 mm or greater. Positron emission tomography/computerized tomography and transrectal ultrasound guided biopsy show similar sensitivity for localization of any cancer focus. Positron emission tomography/computerized tomography does not seem to have any role in extraprostatic extension detection. Studies of diagnostic accuracy (as opposed to tumor localization) are needed in patients with suspected prostate cancer to see whether positron emission tomography/computerized tomography could have a role in not selected patients.

Abstract: Tumoral dissemination of ovarian cancer most commonly occurs through the intra-peritoneal route; nevertheless, although it is rare, ovarian cancer may also metastasise through the lymphatic channels. Lymphatic diffusion of ovarian cancer usually involves pelvic and retro-peritoneal lymph nodes. Extra-abdominal lymph nodes are rarely involved and their detection may represent a challenge for the oncologist. We describe here two patients studied for ovarian cancer by [18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT): one case during pre-operative staging, the other for restaging after surgery. In both cases PET examination identified extraabdominal lymph node tumoral spread in the left supra-clavicular space; biopsy led to a final diagnosis of recurrent ovarian cancer. Previous reports in the literature on tumoral spread of ovarian cancer to the supra-clavicular nodes are rare, however this possible site of metastatic involvement has to be kept in mind by oncologists and our data show that the 18F-FDG PET/CT may be useful to disclose this unusual supra-diaphragmatic lymphatic diffusion of metastatic lymphatic ovarian cancer.

Abstract: BACKGROUND: Exercise-induced alteration in renal function has been described in patients with essential hypertension. The aim of our study was to assess the significance of adopting a supine posture and the degree of workload required to induce these changes in patients with essential hypertension. The second aim was to assess whether the severity of hypertension had any influence on the development of exercise related renal dysfunction. MATERIAL AND METHODS: Fifteen patients were studied (nine patients with mild and untreated hypertension and six patients with drug resistant hypertension). Exercise renography was carried out using a cycloergometer with the patient lying in supine posture and a target exercise rate of 20 bpm over baseline rate. Each patient was injected with 100 MBq of 99mTc-MAG3 and renography was carried out for 20 minutes. Renography was repeated in rest condition only when an abnormality was observed in exercise scans. RESULTS: Exercise renography was normal in 12 patients, while in 3 patients minor abnormalities were observed during exercise related to a minimal degree of pelvic dilatation. These changes remained substantially unmodified at rest. In none of the 15 patients did we find positive studies (i.e. reversible exercise induced prolongation of tracer transit caused by cortical retention). There was no difference in the results between patients with mild or severe hypertension. CONCLUSIONS: Our results are different from previous reports on exercise renography since different groups have demonstrated exercise-induced renal dysfunction in the majority of patients with essential hypertension. The main differences between our protocol and that adopted in the literature relate to posture during exercise (upright vs. supine) and degree of workload (minor in supine exercise with less workload). These differences may have contributed to our results but further and larger studies are required to address the pathophysiological basis of exercise-induced alteration in renal function in association with essential hypertension.

Abstract:

Abstract: PURPOSE: Metastatic cancers of unknown primary origin are characterised by a poor prognosis, with a survival rate from diagnosis of approximately 12 months. Conventional radiological imaging allows detection of 20%-27% of primary cancers, whereas the detection rate with positron emission tomography (PET) is 24%-40%. The aim of this study was to assess the role of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) in the identification of occult primary cancers. MATERIALS AND METHODS: The study population consisted of 38 consecutive patients with histologically proven metastatic disease and negative or nonconclusive conventional diagnostic procedures. All patients were studied by 18F-FDG PET performed according to the standard procedure (6 h of fasting, intravenous injection of 370 MBq 18F-FDG, and image acquisition with a PET/CT scanner for 4 min per bed position). RESULTS: 18F-FDG-PET/CT detected the occult primary cancer in 20 cases (53%), showing higher sensitivity than that reported for any other imaging modality, including PET. CONCLUSIONS: The encouraging results, if validated by larger series, support the use of PET/CT in patients with carcinoma of unknown primary origin and negative conventional imaging results.

Abstract: Metastatic bone lesions are exceptional at diagnosis in germ cell tumors (GCTs). Bone involvement is usually a late event combined with synchronous metastasis in the retroperitoneal lymph nodes, lung and liver. Bone examination is not considered a standard procedure in the staging of GCTs, and this may contribute to underestimation of the real proportion of bone metastases. Here we report a case of nonseminomatous GCT of the testis with a synchronous, symptomatic, solitary pubic bone metastasis that was completely controlled by systemic chemotherapy and locoregional radiation therapy. Solitary bone metastases from GCTs seem to be chemosensitive and radiosensitive, but we do not know their prognostic value. We reviewed the literature where 3 similar cases have been reported. We propose individualized management for symptomatic GCT patients including bone scintigraphy and/or PET examination at diagnosis and a combined cytotoxic approach with chemotherapy and radiation therapy.

Abstract: This paper aims at discussing the utility of 18F-FDG PET/CT in the evaluation of paediatric solid extracranial tumours. Following a brief discussion of the basic principles and methodology of PET/CT system, it reviews the main characteristics of the tumours that can be visualised with 18F-FDG PET and presents examples of cases where the combined use of 18F-FDG PET/CT fusion imaging helped in the management of patients. It will also discuss the physiologic biodistribution of 18F-FDG, outlining the normal variants in the paediatric patients that may lead to misinterpretation.

Abstract: To evaluate the sensitivity of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 32 patients with a histological diagnosis of extra-nodal MALT lymphoma were referred to the PET Centers in the last 2 years (2003 - 2004) and scanned with 18F-FDG-PET following standard procedures. Overall, the results of 50 18F-FDG-PET scans performed in either active disease state or in complete remission were reviewed. Sites of primary disease included stomach, lung, parotid, skin, orbit, mandible, esophagus and uterus. This study retrospectively enrolled 26 patients with known active disease. 18F-FDG-PET was true positive (TP) in 21/26 patients and false negative (FN) in 5/26. Sensitivity of 18F FDG-PET for extra-nodal MALT was 81%. The data show that 18FDG-PET is a useful diagnostic tool in order to stage, restage or monitor disease in patients with extra-nodal MALT lymphoma.

Abstract: BACKGROUND: Integrated positron emission tomography/computed tomography (PET/CT) systems represent a major development allowing functional and anatomical information to be acquired in a single examination session and therefore providing a more accurate definition of suspected lesion characteristics. Together with the increasing number of clinical settings in which PET/CT scans have been advocated, however, pitfalls in image interpretation have been reported. METHODS: Four female subjects presenting a focal area of increased F-fluorodeoxyglucose (F-FDG) uptake with no evidence of a corresponding CT abnormality were included in the study. PET/CT scans were performed in all cases after the administration of 5.3 MBq . kg of F-FDG through a venous cannula. RESULTS: Focal high uptake of F-FDG was observed in lung lesions without anatomical counterparts on CT in four female cases. The only common feature to all was the paravenous injection of the radiotracer. CONCLUSION: The lesions detected by PET may be related to distal lung microembolism originating from the site of paravenous injection.

Abstract: OBJECTIVE: To evaluate the prevalence and scan interpretation criteria useful in identifying non-tumoural F-FDG focal uptakes (potential pitfalls) in patients who had been previously treated for a malignant lymphoma studied by positron emission tomography (PET). MATERIALS: Nine hundred and ninety-six consecutive PET scans obtained in 706 patients with malignant lymphoma were reviewed. All patients had been previously treated by first-line chemo-radiotherapy, plus surgery when required, and were then studied by FDG PET to investigate suspected recurrence at doubtful or inconclusive conventional radiological imaging (ultrasound, computed tomography, magnetic resonance imaging). PET was obtained with patients in the fasted condition and after i.v. injection of 370 MBq of F-FDG; imaging was acquired 60-90 min later. In patients with focal FDG uptake the final diagnosis was reached on the basis of histological findings or long-term follow-up. RESULTS: Thirty-one of 134 PET scans (23.1%) showing focal FDG uptake were diagnosed as non-tumoural radiotracer uptake, related to the presence of brown fat in seven cases, thymic hyperplasia in five, muscles contraction in four, lymph node unspecific inflammation in four, mediastinal/pulmonary unspecific inflammation in four, gastritis in two, colitis in two, bacterial abscess in one, lactating breast in one, and herpes zoster in one. Each of the above cited situations has been reported in the literature, generally in the form of sporadic reports, as a potential cause of misinterpretation (false positive) in reading a PET scan with the potential for incorrect patient management. An accurate diagnosis in these patients was important for the following therapeutic decision making. CONCLUSIONS: In the whole series of patients with treated malignant lymphoma, the prevalence of non-tumoural FDG focal uptake during follow-up was relatively low (3.1%); conversely, it was relatively high when considering the sub-group of 'positive' PET only (23.1%). The importance of knowing these situations in order to avoid misinterpretation in reading PET scans needs to be emphasized. In this light, an accurate patient's history and a skilful nuclear medicine physician are very important factors. For the same purpose, it is reasonable to think that the use of hybrid PET/CT tomographs could also play an important role in helping to identify non-tumoural FDG focal uptake.

Abstract: PURPOSE: The aim of this study was to evaluate the significance of increased uptake of 18F-fluorodeoxyglucose (FDG) in patients with malignant lymphoma (ML) studied by positron emission tomography (PET). METHODS: A total of 1,120 consecutive scans carried out in 848 patients were reviewed; all patients had a diagnosis of ML [574 non-Hodgkin's lymphoma (NHL) and 274 Hodgkin's disease (HD)] and were studied at completion of therapy, for suspected recurrence or during follow-up. PET was carried out after intravenous injection of 370 MBq of 18F-FDG; images were recorded after 60-90 min. Patients were selected whose reports indicated areas of increased FDG uptake. PET findings were considered positive for lymphomatous localisation when uptake occurred at sites of previous disease, in asymmetrical lymph nodes or in nodes unlikely to be affected by inflammation (mediastinal, except for hilar, and abdominal). PET findings were adjudged negative for neoplastic localisations in the following instances: physiological uptake (urinary, muscular, thymic or gastrointestinal in patients without MALT), symmetrical nodal uptake, uptake in lesions unrelated to lymphoma that had already been identified by other imaging methods at the time of PET scan, uptake at sites atypical for lymphoma, very low uptake and non-focal uptake. PET findings were compared with the results of other diagnostic procedures (including CT and ultrasound), biopsy findings and follow-up data. RESULTS: Overall, 354 scans (in 256 patients) showed increased FDG uptake (244 scans in NHL and 110 in HD): in 286 cases, FDG uptake was considered pathological and indicative of ML, in 41 cases the findings were described as uncertain or equivocal and in 37 cases, FDG uptake was considered unrelated to ML (in ten scans, concurrent findings of abnormal FDG uptake attributed to ML and uptake assigned to other causes were obtained) . Of the 286 patients with positive PET findings, 274 (95.8%) were found to have residual or recurrent ML (i.e. true positives). Four of the 41 patients with inconclusive findings turned out to have ML, while in 13 patients, pathological processes other than ML could be identified as the cause of FDG uptake. ML was excluded in all patients with findings reported as non-pathological (100% true-negative rate). Therefore, the false-positive rate in our series was about 5%. The main cause of increased FDG uptake mimicking ML was inflammation. CONCLUSION: Our data confirm that 18F-FDG-PET has very high but not absolute specificity for ML. As already suggested, increased FDG uptake may also be observed in patients without active disease; in most cases, however, non-pathological FDG accumulation is properly identified. Less frequently, inconclusive scans are encountered; these cases are usually caused by inflammation, which subsequently resolves.

Abstract: This study evaluated the potential usefulness of (11)C-choline PET/CT for detection and localization of tumors within the prostate. We used the results of step-section histopathologic examination as the standard of reference. METHODS: The results were analyzed on a sextant basis. We reviewed the results of the (11)C-choline PET/CT scans of 36 patients with prostate cancer and of 5 control subjects with bladder cancer. All patients underwent (11)C-choline PET/CT and, subsequently, radical prostatectomy with lymph node dissection within 1 mo. (11)C-Choline PET/CT scans were obtained 5-10 min after intravenous injection of 370-555 MBq of (11)C-choline. Images were reviewed visually and semiquantitatively using maximum SUV and tumor-to-background ratio. RESULTS: On a sextant basis, histopathologic analysis detected cancer foci in 143 of 216 sextants; high-grade prostate intraepithelial neoplasm foci were detected in 89 of 216 sextants (in 59 sextants in association with carcinoma, in 30 sextants alone), acute prostatitis was detected in 7 of 216 sextants (in 3 sextants in association with carcinoma, in 4 sextants alone), and 39 of 216 sextants were normal. PET/CT demonstrated focal (11)C-choline uptake in 108 sextants (94 of which involved tumor), and 108 sextants showed no abnormal (11)C-choline uptake (49 of which were false negative). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 66%, 81%, 71%, 87%, and 55%, respectively. In the 5 control subjects, high-grade prostate intraepithelial neoplasm was detected at histologic examination in 16 of 30 sextants. PET/CT showed increased (11)C-choline uptake in 5 of 16 sextants. CONCLUSION: This study demonstrated the feasibility of using (11)C-choline PET/CT to identify cancer foci within the prostate. However, we also found that (11)C-choline PET/CT has a relative high rate of false-negative results on a sextant basis and that prostatic disorders other than cancer may accumulate (11)C-choline. Therefore, our data do not support the routine use of PET/CT with (11)C-choline as a first-line screening procedure for prostate cancer in men at high risk.

Abstract: PURPOSE: Metastatic cancer of unknown primary origin is a syndrome characterised by a poor prognosis, with a typical survival rate from diagnosis of no longer than 1 year. Only 20-27% of primary tumours are identified by conventional radiological imaging. By contrast, it has been reported that 18F-fluorodeoxyglucose positron emission tomography (FDG PET) allows the identification of 24-40% of otherwise unrecognised primary tumours. To our knowledge, the studies on this topic have been conducted using 18F-FDG PET imaging alone. The aim of this study was to evaluate the potential additional diagnostic role of fused 18F-FDG PET-CT imaging for the detection of metastatic occult primary tumours. METHODS: The study population consisted of 21 consecutive patients with biopsy-proven metastatic disease and negative conventional diagnostic procedures. Each patient underwent a PET scan, carried out according to a standard procedure (6 h of fasting, i.v. injection of 370 MBq of 18F-FDG and image acquisition with a dedicated PET-CT scanner for 4 min per bed position). RESULTS: 18F-FDG PET-CT detected the occult primary tumour in 12 patients (57% of cases), providing a detection rate higher than that reported with any other imaging modality, including conventional 18F-FDG PET. CONCLUSION: The favourable results of this study need to be confirmed in larger patient populations with long-term follow-up.

Abstract: BACKGROUND: Despite being a relatively rare disease, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next two decades due to the long time interval elapsing between exposure to causative factors, mainly asbestos, and disease onset. Early disease stages have been reported to benefit from radical surgery. In more advanced disease stages, a multimodality treatment, including various combinations of chemotherapy, external radiotherapy and surgery, may provide some favourable results though the prognosis remains poor. In this regard, an accurate pre-treatment staging plays an important role in offering patients a more appropriate therapeutic planning. In some preliminary studies, (18)F-FDG PET has proven to be able to provide useful information for staging purpose, especially for the detection of metastatic spread to lymph nodes and distant sites. MATERIAL AND METHODS: In the present study, we investigated 15 consecutive patients with histologically proven MPM by means of conventional 2-mm thickness whole-body CT scan with and without contrast medium in comparison with wholebody (18)F-FDG PET/CT fusion imaging. RESULTS: (18)F-FDG PET/CT did not provide additional information about the primary tumour (T) compared to CT scan, but identified a higher number of metastatic mediastinal lymph nodes (N) in 6 patients (40% of cases) and unknown metastatic disease to distant sites (M) in 3 patients (20% of cases). On the basis of PET/CT findings, treatment planning was changed in 5 patients (33.3% of cases). CONCLUSIONS: Our data show that (18)F-FDG PET/CT fusion imaging can play a relevant role in the staging and treatment planning of MPM patients.

Abstract: AIM: The aim of the present study was to assess the accuracy of an hybrid PET/CT scanner in the evaluation of newly diagnosed parotid masses, comparing the results with those reported in the literature with using PET scanners only. METHODS: The potential role of 18F-FDG PET/CT in distinguishing benign from malignant parotid masses in 14 consecutive patients was investigated. All patients were preoperatively evaluated by means of ultrasound (US), US-guided fine needle aspiration (FNA) cytology, computed tomography (CT) scan, magnetic resonance imaging (MRI) and 18F-FDG PET/CT. For To interpreting FDG PET findings, the right to left parotid (R/L) SUV max ratio was calculated in a group of 54 patients without evidence of parotideal disease (mean+/-SD = 1+/-0.2; range = 0.8-1.2); considering the R/L SUV max ratio, focal or diffuse uptakes <0.8 or >1.2 were considered as potentially pathological. RESULTS: Imaging data were compared with surgical and histopathological findings. At FDG PET/CT, 9 false positive cases were found (8 Warthin's tumours, 1 pleomorphic adenoma), 1 false negative (acinar cell carcinoma), 4 true negative (1 Warthin's tumour, 1 pleomorphic adenoma, 1 lymph epithelial cyst, 1 parotid inflammation) whereas there was no case of true positive. The global accuracy of FGD PET/CT was rather low = at 29%. CONCLUSIONS: In agreement with other preliminary reports in which the FDG PET without CT fusion imaging was used, in our experience 18F-FDG PET/CT did not prove to play a significant role in differential diagnosis (benign vs malignant) of parotid masses. Further studies collecting larger groups of patients are needed to further elucidate this observation.

Abstract: An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41 CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0 out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET(-)/CT(+) (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

Abstract: OBJECTIVE: The aim of this study was to evaluate the rate of postactinic inflammatory alterations that could lead to false-positive results in FDG-PET images, in a group of lymphoma patients studied with positron emission tomography (PET) early after the end of radiation therapy. MATERIALS AND METHODS: Sixteen (16) consecutive patients were referred to our center for malignant lymphoma; 14 of 16 patients had a mediastinal bulky mass at diagnosis. Each patient underwent chemotherapy and then radiotherapy (RT): for clinical reasons, shortly after RT (range, 25-56 days; mean, 38.7 days) a FDG PET scan was required to evaluate the effect of therapy. We intravenously injected 370 MBq of 18F-FDG, and after 60-90 minutes we recorded images. RESULTS: Despite a relatively short time after RT, there was no pathological tracer uptake in 13 of 16 patients. In 3 cases, a mild increase in FDG uptake was observed, but no findings which would lead to a false-positive diagnosis. In 2 of 3 cases, postactinic pneumopathy was diagnosed (PET scan performed 51 and 52 days after RT); while in 1 patient, soft-tissue inflammation was present (PET scan performed 42 days after RT). CONCLUSION: Our data indicates that the rate of postactinic PET inflammatory alterations in lymphoma patients is not very high and appear to be not strictly linked to the elapsed time since the end of RT treatment.

Abstract: Malignant Pleural Mesothelioma (MPM) is a relatively rare neoplasia characterized by a poor prognosis. Recent studies show that new therapeutic approaches can lead to an improvement in life quality and to a prolonged survival; therefore, proper evaluation of MPM before, as well as after, therapy, is needed. The aim of this study was to evaluate the impact of 18F-FDG photon emission tomography (PET) scan compared to computed tomography (CT) findings in patients affected by MPM, whether untreated or already treated. We studied 15 consecutive patients (13 male and 2 female) with a histological diagnosis of MPM, with a mean age of 69.9 years (range: 38-78 years old) and a recent total-body CT scan. Five (5) patients were studied for staging, while 10 patients were studied after therapy. An FDG PET scan was carried out 60 minutes after an intravenous (i.v.) injection of 370 MBq of 18F-FDG. For each patient, we compared the PET stage to the CT stage, and evaluated the role of PET in choosing a therapeutic approach. In 9 of 15 (60%) patients, there was no difference between the PET and the CT stage. In 2 of 15 (13%) patients, PET upstaged the disease, while in 4 of 15 (27%) patients PET downstaged MPM. According to these results, patient management was changed in 3 cases. Specifically, 1 patient was excluded from surgery, and 2 patients had different chemotherapy. These data suggest that PET is useful in the evaluation of MPM, giving additional data that can clarify doubtful CT findings, especially regarding lymph node involvement and distant lesions. In conclusion, FDG PET was found to play a worth-while role in patient management.

Abstract: This study aims to assess the influence of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) detection of recurrent disease on the management of patients with colorectal cancer and suspected recurrence. One hundred and twenty patients with suspected recurrence were studied with FDG-PET. Fifty-eight patients were referred for FDG-PET because of the elevation of serum tumour markers. Thirty-one patients were referred because of inconclusive results of conventional imaging modalities. Twenty-five patients had known recurrence and were referred for pre-surgical assessment. Six patients were referred because of abdominal pain. A major management change was considered when, as a consequence of FDG-PET results, medical treatment was changed to surgical, or surgical to medical or to no treatment. A minor management change was considered when changes were made within a treatment modality. Of the 58 patients with elevated serum carcinoembryonic antigen (CEA), FDG-PET detected recurrence and led to a major management change in 34 (58%). Eighteen underwent curative surgery and 16 were treated with systemic therapy. Of the 31 patients evaluated because of inconclusive results of conventional imaging modalities, FDG-PET was positive for recurrence in 24 and negative in seven. A major management change took place in 14 patients (45%). Of the 25 patients evaluated to rule out other sites of disease before surgery, FDG-PET did not show any other site of recurrence in 13 (52%) and showed more lesions in the remaining patients. Major management change took place in eight patients (32%). Overall, in the 120 patients studied, FDG-PET resulted in major management changes in 58 (48%), minor changes in four (3%) and no change in 54 (45%). It can be concluded that FDG-PET has a significant impact on the management of patients with suspected recurrence of colorectal cancer. FDG-PET detection of recurrence frequently allows curative surgical intervention. The early identification of distant metastases may also facilitate the implementation of systemic treatment.

Abstract: PURPOSE: The aim of this work was to determine the standard uptake value (SUV) threshold for differentiating malignant from benign bone lesions. MATERIAL AND METHODS: Ninety-nine bone sites in 33 patients who had undergone a 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) study for cancer evaluation were studied. In addition to FDG-PET, a bone scan and at least two of the following determinations: magnetic resonance imaging (MRI), computed tomography (CT), and x-ray were conducted in each patient. The bone lesions were considered positive for malignancy if confirmed by clinical follow-up or a high degree of suspicion based on the positive results of at least three (which must include bone scan) out of four other imaging modalities. By these criteria, 39 lesions were considered positive and 60 were considered negative. The SUV values were classified as positive or negative using 61 different values of threshold (range from 1.0 to 7.0). These results were compared with the positive criteria above and reclassified as true positive, true negative, false positive, and false negative. The true-positive fraction and false-positive fraction were calculated for each threshold value. The receiver operating characteristic (ROC) curve was drawn and the best value was determined by visual analysis. RESULTS: The SUV threshold was considered 2.5. Twenty-nine out of 39 bone lesions classified as positive showed a SUV > 2.5. Of the 10 false-negative lesions, seven showed a SUV between 1.1 and 2.0, and three were not detected. Fifty-six out of 60 lesions classified as negative showed a SUV < 2.5. Four lesions were false positive: one was a rib fracture and three were severe degenerative changes in the lumbar spine. Using an SUV threshold of 2.5, the sensitivity was 74.3% and the specificity was 93.3%. CONCLUSION: In our patient population, the optimal SUV to classify a bone lesion as malignant or benign is 2.5.