Synthesis and preliminary biological evaluation of carbonic anhydrase Ⅸ-targeted PET imaging probe
10.3760/cma.j.cn321828-20241108-00390
- VernacularTitle:碳酸酐酶Ⅸ靶向PET显像探针的合成及初步生物学评价
- Author:
Qianhui WANG
1
;
Bingqing QIU
;
Huan PENG
;
Ying PENG
;
Jianguo LIN
;
Ling QIU
Author Information
1. 江南大学化学与材料工程学院，无锡 214122
- Publication Type:Journal Article
- Keywords:
Carcinoma, renal cell;
Carbonic anhydrase Ⅸ;
Isotope labeling;
Fluorine radioisotopes;
Positron-emission tomography;
Tumor cells, cultured;
Mice, nude
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2025;45(3):169-174
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To design and synthesize a 18F-labeled small molecule PET imaging probe targeting carbonic anhydrase Ⅸ (CAⅨ), named as 18F-single-acetazolamide (SAZ), and to evaluate its biological properties preliminarily. Methods:Acetazolamide was used as raw material to synthesize the precursor SAZ, and the target probe 18F-SAZ was obtained through nucleophilic substitution and other reactions. The radiochemical yield, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-SAZ were determined. Cancer cell lines OS-RC-2 (CAⅨ-positive) and HCT116 (CAⅨ-negative) were used for cell uptake experiments, and corresponding tumor-bearing mice were constructed for microPET imaging. Biodistribution of the probe in OS-RC-2 tumor-bearing mice was analyzed. The difference among groups was analyzed by repeated measures analysis of variance and Bonferroni method. Results:The probe 18F-SAZ was successfully prepared with the labelling yield of (5.60±0.51)%, specific activity of (7.90±0.62)MBq/nmol, radiochemical purity more than 99%, and the lipid water partition coefficient log P of -0.38±0.01. After incubation with PBS or mouse serum for 4 h, the radiochemical purity was still more than 99%. The uptake of 18F-SAZ in OS-RC-2 cells reached (1.47±0.24) percentage of the added radioactivity dose (%AD) at 30min, which was significantly higher than the uptake in the blocked group and that in HCT116 cells ((0.60±0.07)%AD, (0.50±0.05)%AD; F=24.31, P values: 0.012, 0.013 (Bonferroni correction method)). The results of microPET imaging showed that the uptake of 18F-SAZ in OS-RC-2 tumors reached the maximum at 30min ((2.92±0.07) percentage activity of injection dose per gram of tissue (%ID/g)), while the maximum uptakes in the blocked group and HCT116 tumors were only (1.36±0.02) and (1.12±0.07)%ID/g, respectively. 18F-SAZ was mainly distributed in tumors and organs including kidney, intestine, liver, stomach in OS-RC-2 tumor-bearing mice. Conclusions:The probe 18F-SAZ is successfully synthesized. It has high radiochemical purity and good stability in vitro, and can specifically target tumor cells with high expression of CAⅨ. It is expected to be a new CAⅨ-targeting PET imaging probe.
