Radiosynthesis and in vivo evaluation of a F‐18‐labeled pancreatic islet amyloid inhibitor

Formation of islet amyloid deposits contributes to the progressive loss of beta‐cells in Type 2 diabetes. Islet amyloid is composed of islet amyloid polypeptide (IAPP). [(N‐Me)G 24 , (N‐Me)I 26 ]hIAPP(22–27) peptide was found to bind human IAPP with high‐affinity and inhibit fibrillogenesis. We labeled [(N‐Me)G 24 , (N‐Me)I 26 ]hIAPP(22–27) with fluorine‐18 using N ‐succinimidyl‐4‐[ 18 F]fluorobenzoate. Results from biodistribution studies in healthy CF‐1 mice at 1 h p.i. indicated that 18 F‐peptide was cleared efficiently (0.04±0.02%ID/g remained in blood). The primary route of clearance from the body appears to be hepatobiliary. Radioactivity accumulation in liver, intestine, and kidney was 6.7±2.9, 60.3±18.5, and 0.2±0.0%ID, respectively. Other organs accumulated negligible radioactivity. As normal mice do not develop pancreatic amyloid deposits, only background radioactivity was seen in pancreas. The radio‐HPLC analysis of mouse urine at 2 h p.i. showed that ∼29.3% of injected 18 F‐peptide excreted intact along with two additional metabolite peaks. Dynamic microPET/CT imaging of a CF‐1 mouse injected with 18 F‐peptide indicated that radiotracer was rapidly taken up by liver and most of it moved into intestine within 10 min. The results provide a useful insight into the biological disposition of [(N‐Me)G 24 , (N‐Me)I 26 ]hIAPP(22–27) that is being developed as a pancreatic amyloid inhibitor. Copyright © 2010 John Wiley & Sons, Ltd.