Synthesis and preliminary biological evaluation of estrogen receptor α-targeted PET imaging probe
10.3760/cma.j.cn321828-20240722-00269
- VernacularTitle:雌激素受体α靶向PET显像探针的合成及初步生物学评价
- Author:
Ying PENG
1
;
Panpan CHEN
1
;
Ling QIU
1
;
Jianguo LIN
1
Author Information
1. 国家卫生健康委员会核医学重点实验室、江苏省分子核医学重点实验室、江苏省原子医学研究所，无锡 214063
- Publication Type:Journal Article
- Keywords:
Breast neoplasms;
Estrogen receptor alpha;
Carbolines;
Isotope labeling;
Fluorine radioisotopes;
Positron-emission tomography;
Tumor cells, cultured;
Mice, n
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2025;45(8):452-457
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To synthesize 18F labeled PET imaging probe based on giredestrant (GDC-9545), an estrogen receptor α (ERα) degrader and antagonist, and evaluate its ERα-targeting properties. Methods:The precursor-GDC (PGDC), GDC and 18F-GDC were synthesized. The radiochemical yields, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-GDC were determined. Cellular uptake and blocking assays of 18F-GDC were performed using ERα high-expressing MCF-7 cells and ERα low-expressing MDA-MB-231 cells. MCF-7 and MDA-MB-231 tumor-bearing mice were constructed and microPET imaging was performed. The biodistribution of 18F-GDC in MCF-7 tumor-bearing mice was studied. Data were analyzed by using two-way repeated measures analysis of variance and Bonferroni correction method. Results:PGDC and GDC were successfully prepared with the purity more than 95%. 18F-GDC was successfully synthesized with the labeling yield of (11.25±3.18)%, radiochemical purity more than 98%, specific activity of (140.66±17.20)GBq/μmol and lipid water partition coefficient log P of 2.12±0.13. 18F-GDC was stable in PBS or mouse serum, with the radiochemical purity still more than 98% after 2 h of incubation. After incubation for 60 and 120min, the uptakes of 18F-GDC in MCF-7 cells were significantly higher than those in MDA-MB-231 cells ( F values: 113.78, 369.70, P values: 0.002, 0.001 (Bonferroni correction method)), and could be blocked by GDC. 18F-GDC had a high uptake in MCF-7 tumors and could be blocked by GDC. Tumor uptake at 60 min post-injection was (7.23±0.74) percentage activity of injection dose per gram of tissue (%ID/g) and the tumor/muscle uptake ratio was 2.83±0.29 in MCF-7 tumors, while 18F-GDC had a lower uptake in MDA-MB-231 tumors, with (2.01±0.46)%ID/g at 60min post-injection, and a tumor/muscle uptake ratio of 0.96±0.22 ( F values: 77.28, 55.44, P values: 0.002, 0.006 (Bonferroni correction method)). 18F-GDC was mainly distributed in MCF-7 tumors and organs including heart, liver, spleen, kidney, stomach and intestines. Conclusions:18F-GDC is successfully synthesized, with high radiochemical purity and stability, and can concentrate in the ERα-overexpressing cancer cells and lesion area of xenograft tumor mouse. It presents good image contrast in PET imaging, indicating excellent diagnostic performance.
