18F-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(2)/D(3) receptor (D(2)...
Saved in:
Published in | The Journal of nuclear medicine (1978) Vol. 52; no. 7; pp. 1125 - 1132 |
---|---|
Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.07.2011
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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)/D(3)R)-based PET method to study islet cells in the rat pancreas and in islet cell transplantation.
(18)F-fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D(2)/D(3)R inhibitor haloperidol. After intravenous (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 (18)F-fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of (18)F-fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into the spleen and visualized using (18)F-fallypride PET.
(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(2)/D(3)R-specific. Chemical destruction of islets by streptozotocin decreased (18)F-fallypride binding in pancreas by greater than 50%, paralleling the decrease in insulin immunostaining. Uptake of (18)F-fallypride in the pancreas was confirmed by radiochromatography and was 0.05% injected dose/cm(3) as measured by PET/CT. The ratio of (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 (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.
These studies demonstrate the potential utility of (18)F-fallypride as a PET agent for islet cells. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0161-5505 1535-5667 |
DOI: | 10.2967/jnumed.111.088583 |