br In the cell uptake studies F
In the cell uptake studies, [18F]FPTT showed higher uptake in PR-positive MCF-7 Filipin III than in PR-negative MDA-MB-231 cells, and could be specifically inhibited. Especially, the uptake of [18F]FPTT in PR-negative MDA-MB-231 cells with or without PR inhibitor was not signif-icantly different.
In microPET imaging, PR-positive MCF-7 tumor could be imaged at early time point with good contrast which the highest uptake was reached at 1 h p.i. (3.90 ± 0.20%ID/g). Moreover, the specificity of [18F]FPTT was demonstrated by blocking and PR-negative MDA-MB-231 tumor control studies, respectively. As expected, the reduced liver uptake of [18F]FPTT was obtained leading to a higher target to non-target ratio.
From the biodistribution study, the uterus and ovary uptakes of [18F] FPTT in estrogen-primed immature female SD rats are comparable to that of previously reported [18F]FPTP, [18F]FENP and [18F]FFNP. When compared with the above-mentioned tracers, much lower liver, lung, spleen and other non-specific organs uptakes, while higher muscle
and bone uptakes of [18F]FPTT were observed. Of course, [18F]FPTT also accumulated in the intestine due to its steroid metabolic pathway. The targeting ability of [18F]FPTT to PR had been verified through a se-ries of in vivo and in vitro bio-evaluation and it will be further investi-gated to determine the safety and dose for PR-positive breast cancer imaging.
A novel 18F-labeled ethisterone triazole derivative was designed and successfully synthesized by a one-step nucleophilic substitution reac-tion. In vitro studies showed that [18F]FPTT had moderate lipophilicity with nanomolar binding affinity to PR. Ex vivo biodistribution in estrogen-primed immature female SD rats resulted in high PR-rich tis-sues uptake. In vivo microPET imaging studies indicated that [18F]FPTT had specific uptake in PR-positive MCF-7 tumor with low uptakes in non-target tissues of tumor-bearing mice. The above results showed that [18F]FPTT could be a potent PET tracer for PR targeted breast cancer diagnosis and assess the efficacy of antiestrogen treatment.
This study was financially supported by the National Basic Research Program of China (2014CB744503) and Natural Science Foundation of Fujian Province, China (No. 2016J05200).
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
 Ulaner GA, Riedl CC, Dickler MN, Jhaveri K, Pandit-Taskar N, Weber W. Molecular imaging of biomarkers in breast cancer. J Nucl Med 2016;57(Suppl. 1):53S.  Normanno N, Di MME, De LA, De MA, Giordano A, Perrone F. Mechanisms of endo-crine resistance and novel therapeutic strategies in breast cancer. Endocr Relat Can-cer 2016;12:721–47.
clinical evaluation of a positron emitting progestin ([18F]fluoro 16 alpha methyl 19 norprogesterone) for imaging progesterone receptor positive tu-mours with positron emission tomography. Cancer Lett 1991;59:125–32.
 Pomper MG, Katzenellenbogen JA, Welch MJ, Brodack JW, Mathias CJ. 21 [18F] Fluoro 16α ethyl 19 norprogesteron synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography. J Med Chem 1988;31:1360–3.
 Gao F, Peng C, Li J, Zhuang R, Guo Z, Xu D, et al. Radioiodinated progesterone deriv-ative for progesterone receptor targeting with enhanced nucleus uptake via phenylboronic acid conjugation. J Label Compd Radiopharm 2019. https://doi.org/ 10.1002/jlcr.3741.
 Slooten H-J, Bonsing BA, Hiller AJ, Colbern GT, Dierendonck JH, Cornelisse CJ, et al. Outgrowth of BT-474 human breast cancer cells in immune-deficient mice: a new in vivo model for hormone-dependent breast cancer. Brit J Cancer 1995;72:22–30.  Paquette M, Turcotte E. Measuring estrogen receptor functionality using progester-one receptor PET imaging: rising to the (estradiol) challenge! J Nucl Med 2019; 60:218–9.