Preclinical Imaging Center, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California 92697, USA.
J Nucl Med. 2011 Jul;52(7):1125-32. doi: 10.2967/jnumed.111.088583. Epub 2011 Jun 16.
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.
描述一种新型的基于多巴胺 D2/ D3 受体（D2/ D3R）的 PET 方法，用于研究大鼠胰腺中的胰岛细胞和胰岛细胞移植。
（1）在不存在和存在 D2/ D3R 抑制剂氟哌啶醇的情况下，评估（18）F-法利培醇与分离的大鼠胰岛和胰腺的结合。静脉内给予（18）F-法利培醇（28-37MBq）后，将氟哌啶醇预处理的正常大鼠和大鼠在 PET/CT 扫描仪中进行成像，并随后对胰腺中（18）F-法利培醇的定位进行离体研究。使用链脲佐菌素治疗的糖尿病大鼠模型研究（18）F-法利培醇在体外和体内的胰腺定位。将大鼠胰岛细胞移植到脾脏中，并使用（18）F-法利培醇 PET 进行可视化。
（18）F-法利培醇与分离的胰岛细胞和胰腺切片结合，具有约 4 的内分泌或外分泌选择性；氟哌啶醇降低了选择性，表明结合是 D2/ D3R 特异性的。链脲佐菌素对胰岛的化学破坏使胰腺中（18）F-法利培醇的结合减少了 50%以上，与胰岛素免疫染色的减少相平行。通过放射性色谱法证实了（18）F-法利培醇在胰腺中的摄取，通过 PET/CT 测量为 0.05%注入剂量/cm3。胰腺中（18）F-法利培醇摄取与参考组织（竖脊肌）的比值为 5.5。通过（18）F-法利培醇在体内可视化移植到脾脏的大鼠胰岛，并通过免疫染色证实。与未移植大鼠的 2.8 相比，移植到脾脏的胰岛与竖脊肌的比值大于 5。
这些研究表明（18）F-法利培醇作为一种用于胰岛细胞的 PET 示踪剂具有潜在的应用价值。
