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  • br In the cell uptake studies F

    2019-09-16


    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 Filipin III 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.
    5. Conclusion
    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.
    Acknowledgments
    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.
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