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  • MF498 br Conclusion A novel F FPTT probe based on ethisteron

    2019-09-16


    Conclusion: A novel [18F]FPTT probe based on ethisterone modification could be a potential diagnostic agent for PR-positive breast cancer.
    1. Introduction
    A large number of clinical trials have proved that the key to the prog-nosis of malignant tumors lies in the early detection, diagnosis and treatment of diseases [1,2]. In particular, the early diagnosis of breast cancer will help to alleviate the pain of patients and improve the prog-nosis of cancer [3]. Although immunohistochemical methods are cur-rently used to assess the hormone receptor status of metastatic tumors, there are many limitations in determining the hormone recep-tor status of metastatic tumors [4,5]. For example, the location of the ex-amination is not suitable for biopsy, sample processing (especially decalcification) will also produce false negative results, as well as intratumoral and tumor stroma heterogeneity. Molecular imaging has
    Corresponding authors at: School of Public Health, Xiamen University, 4221-116 Xiang'an South Rd., Xiang'an District, Xiamen 361102, China. E-mail addresses: [email protected] (R. Zhuang), [email protected] (X. Zhang).
    been widely used to improve the specificity and quantification of screening and early diagnosis, centralized and personalized treatment, and follow-up of early treatment [6–8].
    Accurate early detection of tumors requires efficient and safe molec-ular imaging probes [9]. According to the MF498 characteristics of breast cancer receptors, targeted endocrine therapy has become an at-tractive therapeutic option in the diagnosis and treatment of breast can-cer [10,11]. Progesterone receptor (PR) is closely related to the invasiveness, prognosis and efficacy of hormone-related diseases such as breast cancer, ovarian cancer, uterine cancer and endometriosis [12,13]. In recent years, many radiolabeled PR targeted probes for PET imaging have been reported and evaluated ([18F]FMNP, MF498 [18F]FENP, [18F]FPTP, [18F]FFNP, [18F]EAEF, et al.) [14–19]. Most of them use modi-fied steroid structures as probes targeting PR, such as testosterone, pro-gesterone and 19-nortestosterone, and different modifications of these structures. This is due to the fact that most receptors have a high affinity for their cognate ligands. Ethisterone is a natural progesterone
    derivative, which has a strong affinity for PR, and its alkynyl group can be easily modified compared with other steroids [19]. Of course, be-sides, ethisterone is also very popular modification group on other im-aging agents targeting PR [20]. 18F (t1/2 = 109.8 min) is a suitable radionuclide for PET imaging due to its advantages of high positron decay (97%), low positron energy (0.634 MeV) and smaller atomic ra-dius. In addition, the inherent advantages of PET imaging which has high sensitivity, good spatial resolution and quantitative and dynamic monitoring has become a non-invasive method for breast cancer diag-nosis [21,22]. In this study, radionuclide 18F was incorporated into ethisterone derivative to develop a novel radiotracer ([18F]FPTT) for PR targeting, the physicochemical properties, binding affinity, and PET imaging feasibility of [18F]FPTT for PR-positive breast cancer early diag-nosis were evaluated in vivo and in vitro, respectively.
    2. Materials and methods
    2.1. General methods
    All reagents and solvents were purchased from commercial sup-pliers. High performance liquid chromatography (HPLC) analysis was performed on an UltiMate 3000 pump (DIONEX) and an UltiMate 3000 UV absorbance full λ detector (DIONEX) combined with a flow-counter radioactivity detector (Bioscan, USA). Characterization of inter-mediates and final products of FPTT including 1H NMR and 13C NMR by nuclear magnetic resonance spectrometer (Wuhan Zhongke Niujin Magnetic Resonance Technology Co., Ltd, BIXI-I 400) and mass spec-trometry (Waters, Xevo, G2-XS TOF).