Preparation and evaluation of PET tracer 18F-JR-1001 targeting cannabinoid type 1 receptor
10.3760/cma.j.cn321828-20240905-00313
- VernacularTitle:靶向大麻素1型受体的PET显像剂 18F-JR-1001的制备与评价
- Author:
Dilong MAO
1
;
Yangyang XU
;
Junwei CHEN
;
Wanli HE
;
Chentao JIN
;
Xiaofen MA
;
Hong ZHANG
;
Yi WEI
;
Shuxia CAO
;
Qiaozhen CHEN
;
Qinggang HE
Author Information
1. 浙江大学化学工程与生物工程学院，杭州 310058
- Publication Type:Journal Article
- Keywords:
Nervous system;
Radiopharmaceuticals;
Fluorine radioisotopes;
Receptor, cannabinoid, CB1;
Positron-emission tomography;
Rats;
JR-1001
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2025;45(10):617-622
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.
