Abstract: CONTEXT: Due to the restricted accessibility of pancreatic tissue in living man, direct analysis of the events preceding development of autoimmune changes in the pancreas has been problematic. In vivo imaging of insulitis might markedly increase understanding of the events and timing of the events that are necessary for the progression toward overt type 1 diabetes. DESIGN: To evaluate possibilities to visualize insulitis in man in vivo with positron emission tomography, we studied 12 male patients (age 26 +/- 7 yr) with newly diagnosed type 1 diabetes (duration range 0-7 months) and nine age- and sex-matched healthy controls after an overnight fast using 2-[(18)F]fluoro-2-deoxy-D-glucose and [(11)C]methionine. For definition of the regions of interest, pancreas was localized with magnetic resonance imaging or computed tomography-positron emission tomography. RESULTS: Glucose uptake to the pancreas was markedly higher in the patients with type 1 diabetes than in the healthy controls (22.9 +/- 6.4 vs. 17.8 +/- 6.0 micromol/kg.min, P = 0.039). Glucose uptake to the pancreas of the patients was inversely associated with the duration of diabetes (r = -0.58; P = 0.024), so that in patients with newly diagnosed type 1 diabetes, glucose uptake was higher than in the healthy controls or patients with long duration of diabetes. Methionine uptake to the pancreas of the patients was similar as in the controls (3.7 +/- 1.9 vs. 4.6 +/- 2.4 micromol/kg.min, P = 0.21). CONCLUSIONS: In patients with type 1 diabetes, glucose uptake to the pancreas is enhanced at or soon after the time of diagnosis.

Abstract: To evaluate the potential of in vivo imaging of accumulation of lymphocytes to islets of Langerhans (insulitis), we compared 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) uptake in the pancreas and pancreatic islets of healthy BALB/c mice, phenotypically healthy NOD mice with insulitis and diabetic NOD mice. [(18)F]FDG was injected i.v. to 14 female BALB/c mice (age 13+/-3 weeks, plasma glucose 8+/-2 mmol/l) and 21 age-matched female NOD mice (plasma glucose 8+/-4 mmol/l, p=0.06). The mice were killed 90-min post injection and distribution of radioactivity was analysed using digital autoradiography. There was no correlation of plasma glucose concentration with the [(18)F]FDG uptake values. Uptake of radioactivity in NOD mice to the islets affected by insulitis was up to 2.3 times higher (p=0.001) than that to unaffected islets in the same pancreas. Uptake to NOD islets with insulitis was also clearly enhanced (1.0-2.3 times higher) compared to the islets in the BALB/c mice. In conclusion, NOD mouse islets with insulitis accumulate [(18)F]FDG markedly more than islets without insulitis or BALB/c islets. However, the relatively small difference in the [(18)F]FDG intensity between healthy and diseased islets, combined with the limited resolution ability of the positron emission tomography (PET), probably prevent the use of [(18)F]FDG in PET studies aiming at in vivo documentation of onset and progression of insulitis and prediabetes in mouse and man.