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

Abstract

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)G24, (N‐Me)I26]hIAPP(22–27) peptide was found to bind human IAPP with high‐affinity and inhibit fibrillogenesis. We labeled [(N‐Me)G24, (N‐Me)I26]hIAPP(22–27) with fluorine‐18 using N‐succinimidyl‐4‐[18F]fluorobenzoate. Results from biodistribution studies in healthy CF‐1 mice at 1 h p.i. indicated that 18F‐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 18F‐peptide excreted intact along with two additional metabolite peaks. Dynamic microPET/CT imaging of a CF‐1 mouse injected with 18F‐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)G24, (N‐Me)I26]hIAPP(22–27) that is being developed as a pancreatic amyloid inhibitor. Copyright © 2010 John Wiley & Sons, Ltd.

Comparison of three 18F-labeled carboxylic acids with 18F-FDG of the differentiation tumor from inflammation in model mice

“…For 18 F-FBA, the biodistribution studies demonstrated that 18 F-FBA had an advantage of rapid clearance in the most tissues. The differences of biodistribution between 18 F-FBA and 18 F-FAC (or 18 F-FPA) could be attributed to the different metabolic pathway, and 18 F-FBA was converted into p - 18 F-fluorohippuric acid derivatives via a glycine-conjugation pathway in the liver and eliminated through the kidneys [ 38 – 40 ]. Meanwhile, 18 F-FBA PET imaging showed the clear contrast between tumor and inflammation lesion with the highest ratios of tumor-to-inflammation as 1.98 ± 0.15.…”

Synthesis and In Vivo Evaluation ofp-18F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET

“…We observed that the major metabolite of 4-18 F-fluorobenzoic acid is excreted rapidly and exclusively in urine as p-18 F-fluorohippurate ( 18 F-PFH) (14). It is known that benzoic acid derivatives are converted in vivo into hippuric acid derivatives via the glycine-conjugation pathway in the liver (15,16).…”