18F-labeled ethisterone derivative for progesterone receptor targeted PET imaging of breast cancer

Abstract Purpose A novel radiolabeled probe 1‑(17‑[ 18 F]fluoro‑3,6,9,12,15‑pentaoxaheptadecyl‑1H‑1,2,3‑triazole testosterone ([ 18 F]FPTT) was synthesized and evaluated for PET imaging of progesterone receptor (PR)-positive breast cancer. Methods The ethinyl group of ethisterone, a PR targeting pharmacophore, was coupled with azide modified PEG-OTs by click chemistry to obtain the labeling precursor. The final [ 18 F]FPTT was synthesized by a one-step nucleophilic substitution reaction with 18 F. The in vitro stabilities of [ 18 F]FPTT in saline or rat serum were determined after 2 h incubation. Then the in vitro cell binding, ex vivo biodistribution and in vivo imaging of [ 18 F]FPTT were further investigated to evaluate the PR targeting ability and feasibility for the diagnosis of PR-positive breast cancer with PET imaging. Results [ 18 F]FPTT was obtained in high decay-corrected radiochemical yield (78 ± 9%) at the end of synthesis. It had high radiochemical purity (>98%) after HPLC purification and good in vitro stability. The molar activity of [ 18 F]FPTT was calculated as 17 GBq/μmol. The microPET imaging of [ 18 F]FPTT in tumor-bearing mice showed much higher tumor uptake in PR-positive MCF-7 tumor (3.9 ± 0.20%ID/g) than that of PR-negative MDA-MB-231 tumor (1.3 ± 0.08%ID/g). The high MCF-7 tumor uptake could be specifically inhibited by blocking with ethisterone (1.3 ± 0.11%ID/g) or [ 19 F]FPTT (2.20 ± 0.17%ID/g), respectively. The biodistribution in estrogen-primed female SD rats of [ 18 F]FPTT showed high uterus and ovary uptakes (8.31 ± 1.74%ID/g and 3.79 ± 0.82%ID/g at 1 h post-injection). The specific uptakes of uterus and ovary in normal rats were 3.52 ± 0.29%ID/g and 3.22 ± 0.50%ID/g respectively and could be inhibited by co-injecting of ethisterone. Conclusion A novel [ 18 F]FPTT probe based on ethisterone modification could be a potential diagnostic agent for PR-positive breast cancer.