^18F标记非甾体类孕酮受体显像剂的制备

Synthesis of ^(18)F-Labelled Nonsteroidal Compound as Potential Progesterone Receptor Imaging Agent

孕酮受体(PR)在乳腺癌中的水平可对乳腺癌的激素治疗进行预测和指导。5-[4-(3-氟丙基)-4-甲基-2-氧-1,4-二氢-2H-苯并[d][1,3]口恶嗪-6-基]-1H-吡咯-2-甲腈(19 FPr-Tanaproget)是Tanaproget的衍生物,它作为孕酮受体激动剂,对PR有高选择性和高亲和性,用放射性核素18F标记、正电子发射断层(PET)技术显像,可通过检测PR的情况,对乳腺癌进行诊断、治疗和预后评估。本实验以自制的氟标记前体,先合成了参比化合物19FPr-Tanaproget,再在氟多功能模块上合成了18 FPr-Tanaproget,经Sep-Pak C-18柱和HPLC分离得到放化纯大于97%的产物。室温下在水中和血清中分别放置6h,放化纯仍大于95%。对标记率影响因素进行了优化,结果显示,最佳标记温度、时间、前体浓度分别为100℃、35min和32.7mmol/L,此条件下总的合成时间为45min,放化产率可达到10.9%(已校正)。

The level of progesterone receptors （PR） in breast tumors can be used to guide the endocrine therapy of breast cancer.As the tanaproget analogue,5-[4-（3-fluoro-propyl）-4-methyl-2-oxo-1,4-dihydro-2 H-benzo[d] [1,3] oxazin-6-yl]-1 H-pyrrole-2-carbonitrile （19 FPr-Tanaproget） is a nonsteroidal progesterone receptor agonist with very high PR binding affinity and high selectivity.Radiolableled with fluorine-18,it might be used to image PR-positive breast tumors by positron emission tomography （PET）.The nonradioactive 19FPr-Tanaproget and radioactive 18 FPr-Tanaproget were synthesized.Crude 18FPr-Tanaproget was separated by Sep-Pak C-18 and semi-preparative HPLC,respectively.The results show that the radiochemical purity is over 97％.It is very stable in vitro within 6 h in saline and serum incubation.The factors influencing labeling efficiency were investigated.The results indicate that the optimal preparation conditions are as follows：the reaction temperature is 100 ℃ ;the reaction time is 35 min; and the concentration of precursor is 32.7 mmol/L.Under this condition,the total synthesis time is 45 min,and the corrected radiochemical yield can achieve to 10.9％.