科研之友
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摘要
Islet cell loss in the pancreas results in diabetes. A noninvasive method that measures islet cell loss and also tracks the fate of transplanted islets would facilitate the development of novel therapeutics and improve the management of diabetes. We describe a novel dopamine D-2/D-3 receptor (D-2/D3R)-based PET method to study islet cells in the rat pancreas and in islet cell transplantation. Methods: F-18-fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D-2/D3R inhibitor haloperidol. After intravenous F-18-fallypride (28-37 MBq) administration, normal rats and rats pre-treated with haloperidol were imaged in a PET/CT scanner and subsequently studied ex vivo for F-18-fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of F-18-fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into the spleen and visualized using F-18-fallypride PET. Results: F-18-fallypride bound to isolated islet cells and pancreatic sections with an endocrine or exocrine selectivity of approximately 4; selectivity was reduced by haloperidol, suggesting that binding was D-2/D3R-specific. Chemical destruction of islets by streptozotocin decreased F-18-fallypride binding in pancreas by greater than 50%, paralleling the decrease in insulin immunostaining. Uptake of F-18-fallypride in the pancreas was confirmed by radiochromatography and was 0.05% injected dose/cm(3) as measured by PET/CT. The ratio of F-18-fallypride uptake in the pancreas to reference tissue (erector spinae muscle) was 5.5. Rat islets transplanted into the spleen were visualized in vivo by F-18-fallypride and confirmed by immunostaining. The ratio of spleen-transplanted islets to erector spinae muscle was greater than 5, compared with a ratio of 2.8 in untransplanted rats. Conclusion: These studies demonstrate the potential utility of F-18-fallypride as a PET agent for islet cells.
- 出版日期2011-7-1
