title: Preliminary evaluation of [18F]AlF-NOTA-MAL-Cys39-exendin-4 in insulinoma with PET.
abstract: BACKGROUND
  High expression of glucagon-like peptide-1 receptor (GLP-1R) in insulinoma supplies a potential drug target for tumor imaging. Exendin-4 can specifically bind to GLP-1R as an agonist and its analogs are extensively used in receptor imaging studies.
  
  
  OBJECTIVE
  A new GLP-1R imaging agent, [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4, was designed and prepared for insulinoma imaging.
  
  
  METHODS
  Cys(39)-exendin-4 was conjugated with NOTA-MAL, then the compound was radiolabeled with [(18)F]AlF complex to obtained [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4. The tumor-targeting characters of the tracer were evaluated in INS-1 cells and BALB/c nude mice models.
  
  
  RESULTS
  [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 can be efficiently produced with a yield of 17.5 ± 3.2% (non-decay corrected) and radiochemical purity of >95%. The IC50 value of displacement [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 with Cys(39)-exendin-4 was 13.52 ± 1.36 nM. PET images showed excellent tumor visualization with high uptake (9.15 ± 1.6%ID/g at 30 min and 7.74 ± 0.87%ID/g at 60 min). The tumor to muscle, pancreas and liver ratios were 63.25, 3.85 and 7.29 at 60 min after injection. GLP-1R binding specificity was demonstrated by co-injection with an excess of unlabeled Cys(39)-exendin-4 and the tumor uptake was found to be reduced significantly.
  
  
  CONCLUSIONS
  [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.
authors.affiliation: a Department of Radiation Oncology , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China .
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: a Department of Radiation Oncology , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China .
authors.forename: Chen
authors.initials: C
authors.lastname: Zhu
authors.affiliation: b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and.
authors.forename: Donghui
authors.initials: D
authors.lastname: Pan
authors.affiliation: c School of Pharmaceutical Science, Zhengzhou University , Zhengzhou , China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and.
authors.forename: Runlin
authors.initials: R
authors.lastname: Yang
authors.affiliation: b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wang
authors.affiliation: b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: a Department of Radiation Oncology , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China .
authors.forename: Xinchen
authors.initials: X
authors.lastname: Sun
authors.affiliation: a Department of Radiation Oncology , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China .|b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and.
authors.forename: Shineng
authors.initials: S
authors.lastname: Luo
authors.affiliation: a Department of Radiation Oncology , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China .|b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D004355:Drug Stability; D000077270:Exenatide; D005260:Female; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring; D007340:Insulinoma / Q000000981:diagnostic imaging*; D008301:Maleimides / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D014688:Venoms / Q000737:chemistry*
chemical_list: D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D008301:Maleimides; D010455:Peptides; D014688:Venoms; C062020:S-(bismaleimidoethyl ether)cysteine; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D000077270:Exenatide; D003545:Cysteine
keywords: Expression; peptide; radio labeling; tumor targeting