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

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^sub 2^/D^sub 3^ recept...

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Veröffentlicht in:The Journal of nuclear medicine (1978) 2011-07, Vol.52 (7), p.1125
Hauptverfasser: Garcia, Adriana, Mirbolooki, Mohammad Reza, Constantinescu, Cristian, Pan, Min-Liang, Sevrioukov, Evegueni, Milne, Norah, Wang, Ping H, Lakey, Jonathan, Chandy, K George, Mukherjee, Jogeshwar
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Sprache:eng
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Zusammenfassung: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^sub 2^/D^sub 3^ receptor (D^sub 2^/D^sub 3^R)-based PET method to study islet cells in the rat pancreas and in islet cell transplantation. Methods: ^sup 18^F-fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D^sub 2^/D^sub 3^R inhibitor haloperidol. After intravenous ^sup 18^F-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 ^sup 18^F-fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of ^sup 18^F-fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into the spleen and visualized using ^sup 18^F-fallypride PET. Results: ^sup 18^F-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^sub 2^/D^sub 3^R-specific. Chemical destruction of islets by streptozotocin decreased ^sup 18^F-fallypride binding in pancreas by greater than 50%, paralleling the decrease in insulin immunostaining. Uptake of ^sup 18^F-fallypride in the pancreas was confirmed by radiochromatography and was 0.05% injected dose/cm^sup 3^ as measured by PET/CT. The ratio of ^sup 18^F-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 ^sup 18^F-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 ^sup 18^F-fallypride as a PET agent for islet cells. [PUBLICATION ABSTRACT]
ISSN:0161-5505
1535-5667