title: Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with (18)F-Al labeled Cys(39)-exendin-4.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Baoming
authors: B
authors: Mi
authors: 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.
authors: Yuping
authors: Y
authors: Xu
authors: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China.
authors: Donghui
authors: D
authors: Pan
authors: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China.
authors: Lizhen
authors: L
authors: Wang
authors: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China.
authors: Runlin
authors: R
authors: Yang
authors: Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University (Wuxi 4th People's Hospital), Wuxi, Jiangsu, 214062, China.
authors: Chunjing
authors: C
authors: Yu
authors: Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University (Wuxi 4th People's Hospital), Wuxi, Jiangsu, 214062, China.
authors: Weixing
authors: W
authors: Wan
authors: Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China. Electronic address: wuyiwei3988@gmail.com.
authors: Yiwei
authors: Y
authors: Wu
authors: 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.
authors: Min
authors: M
authors: Yang
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry / Q000493:pharmacokinetics; D003920:Diabetes Mellitus / Q000000981:diagnostic imaging / Q000378:metabolism*; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D009928:Organ Specificity; D010179:Pancreas / Q000000981:diagnostic imaging / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014688:Venoms / Q000737:chemistry / Q000493:pharmacokinetics*; D051598:Whole Body Imaging
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D019275:Radiopharmaceuticals; D014688:Venoms; D000077270:Exenatide; D003545:Cysteine
keywords: 18F-Al-NOTA-MAL-Cys39-exendin-4; GLP-1R Imaging; PET; Pancreas