Baoming Mi1, Yuping Xu2, Donghui Pan3, Lizhen Wang3, Runlin Yang3, Chunjing Yu4, Weixing Wan4, Yiwei Wu5, Min Yang6. 1. Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China; Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University (Wuxi 4th People's Hospital), Wuxi, Jiangsu, 214062, China. 2. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China; Nanjing Medical University, Nanjing, Jiangsu, 210029, China. 3. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China. 4. Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University (Wuxi 4th People's Hospital), Wuxi, Jiangsu, 214062, China. 5. Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China. Electronic address: wuyiwei3988@gmail.com. 6. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China; Nanjing Medical University, Nanjing, Jiangsu, 210029, China. Electronic address: ymzfk@yahoo.com.hk.
Abstract
PURPOSE: Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, (18)F-Al labeled exendin-4 analog, (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. METHODS: The targeting of (18)F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with (18)F-Al-NOTA-MAL-Cys(39)-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. RESULTS: The pancreas of healthy rats was readily visualized after administration of (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. CONCLUSION: The favorable preclinical data indicated that (18)F-Al-NOTA-MAL-Cys(39)-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells.
PURPOSE:Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, (18)F-Al labeled exendin-4 analog, (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. METHODS: The targeting of (18)F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabeticrats. Rats were injected with (18)F-Al-NOTA-MAL-Cys(39)-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. RESULTS: The pancreas of healthy rats was readily visualized after administration of (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, whereas the pancreas of diabeticrats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabeticrats respectively. Under block, the pancreatic uptakes of non-diabeticrats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. CONCLUSION: The favorable preclinical data indicated that (18)F-Al-NOTA-MAL-Cys(39)-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells.