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

Purpose: A novel radiolabeled probe 1 (17 [F-18]fluoro 3,6,9,12,15 pentaoxaheptadecyl 1H 1,2,3 triazole testosterone ([F-18]FPTT) was synthesized and evaluated for PET imaging of progesterone receptor (PR)-positive breast cancer. Methods: The ethinyl group of e thisterone, a PR targeting pharmacophore, was coupled with azide modified PEG-OTs by click chemistry to obtain the labeling precursor. The final [F-18]FPTT was synthesized by a one-step nudeophilic substitution reaction with F-18. The in vitro stabilities of [F-18]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 [F-18]FPTT were further investigated to evaluate the PR targeting ability and feasibility for the diagnosis of PR-positive breast cancer with PET imaging. Results: [F-18]FPIT 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 [F-18] FPTF was calculated as 17 GBq/mu mol. The microPET imaging of [F-18]FPIT 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 [F-19]FPTT (2.20 = 0.17%ID/g), respectively. The biodistribution in estrogen-primed female SD rats of [F-18]FPTT showed high uterus and ovary uptakes (8.31 +/- 1.74%ID/g and 3.79 +/- 0.82ID/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 [F-18]FPTT probe based on ethisterone modification could be a potential diagnostic agent for PR-positive breast cancer. (C) 2019 Elsevier Inc. All rights reserved.