18F-Fallypride PET of Pancreatic Islets: In Vitro and In Vivo Rodent Studies
18F-Fallypride PET of Pancreatic Islets: In Vitro and In Vivo Rodent Studies
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DOI：
10.2967/jnumed.111.088583
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发表时间：
2011-07-01
影响因子：
9.3
通讯作者：
Mukherjee, Jogeshwar
中科院分区：
文献类型：
--
作者：
Garcia, Adriana;Mirbolooki, Mohammad Reza;Mukherjee, Jogeshwar
胰腺中的胰岛细胞损失导致糖尿病。一种测量胰岛细胞损失并跟踪移植胰岛命运的非侵入性方法将促进新疗法的开发并改善糖尿病的管理。我们描述了一种新的多巴胺D-2/D-3受体（D-2/D3 R）为基础的PET方法来研究胰岛细胞在大鼠胰腺和胰岛细胞移植。方法：在不存在和存在D-2/D3 R抑制剂氟哌啶醇的情况下，评价F-18-氟普利与离体大鼠胰岛和胰腺的结合。在静脉内给予F-18-氟普利（28-37 MBq）后，在PET/CT扫描仪中对正常大鼠和用氟哌啶醇预处理的大鼠进行成像，随后离体研究F-18-氟普利在胰腺中的定位。链脲佐菌素治疗的糖尿病大鼠模型用于研究F-18-fallypride在胰腺中的体外和离体定位。将大鼠胰岛细胞移植到脾脏中，并使用F-18-fallypride PET进行可视化。结果如下：F-18-fallypride与分离的胰岛细胞和胰腺切片结合，内分泌或外分泌选择性约为4;氟哌啶醇降低了选择性，表明结合是D-2/D3 R特异性的。链脲佐菌素对胰岛的化学破坏使胰腺中的F-18-fallypride结合减少了50%以上，与胰岛素免疫染色的减少平行。通过放射性色谱法证实胰腺中F-18-fallypride的摄取，并且通过PET/CT测量为0.05%注射剂量/cm（3）。胰腺与参考组织（竖脊肌）中的F-18-fallypride摄取比率为5.5。通过F-18-fallypride在体内观察移植到脾脏中的大鼠胰岛，并通过免疫染色进行确认。脾移植的胰岛与竖脊肌的比例大于5，而未移植的大鼠的比例为2.8。结论：这些研究证明了F-18-fallypride作为胰岛细胞PET试剂的潜在效用。
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.