18F-Fallypride PET of Pancreatic Islets: In Vitro and In Vivo Rodent Studies

Journal of Nuclear Medicine

Min-Liang Pan¹  Cristian Constantinescu¹  Evegueni Sevrioukov¹  K. George Chandy¹  Ping H. Wang¹  Jonathan Lakey¹  Adriana Garcia¹  Jogeshwar Mukherjee¹  Norah Milne¹  Mohammad Reza Mirbolooki¹ 

关键词: pancreas;    islet cells;    ¹⁸F-fallypride;    PET;    diabetes;   

DOI  :  10.2967/jnumed.111.088583

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 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 D2/D3 receptor (D2/D3R)–based PET method to study islet cells in the rat pancreas and in islet cell transplantation. Methods: 18F-fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D2/D3R inhibitor haloperidol. After intravenous 18F-fallypride (28–37 MBq) administration, normal rats and rats pretreated with haloperidol were imaged in a PET/CT scanner and subsequently studied ex vivo for 18F-fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of 18F-fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into the spleen and visualized using 18F-fallypride PET. Results: 18F-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 D2/D3R-specific. Chemical destruction of islets by streptozotocin decreased 18F-fallypride binding in pancreas by greater than 50%, paralleling the decrease in insulin immunostaining. Uptake of 18F-fallypride in the pancreas was confirmed by radiochromatography and was 0.05% injected dose/cm3 as measured by PET/CT. The ratio of 18F-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 18F-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 18F-fallypride as a PET agent for islet cells.

【 授权许可】

Unknown