Qing Xu1, Chen Zhu1, Yuping Xu2, Donghui Pan2, Ping Liu3, Runlin Yang2, Lizhen Wang2, Fei Chen2, Xinchen Sun1, Shineng Luo1,2, Min Yang1,2. 1. a Department of Radiation Oncology , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China . 2. b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and. 3. c School of Pharmaceutical Science, Zhengzhou University , Zhengzhou , China.
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. PURPOSE: 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. CONCLUSION: [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.
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. PURPOSE: 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. CONCLUSION: [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.
Entities:
Keywords:
Expression; peptide; radio labeling; tumor targeting
Authors: Tom J P Jansen; Sanne A M van Lith; Marti Boss; Maarten Brom; Lieke Joosten; Martin Béhé; Mijke Buitinga; Martin Gotthardt Journal: J Labelled Comp Radiopharm Date: 2019-08 Impact factor: 1.921