Department of Radiology, School of Medicine, State University of New York at Stony Brook, Long Island, Stony Brook, NY, 11974, USA.
Stony Brook Cancer Center, Long Island, Stony Brook, NY, USA.
Sci Rep. 2021 May 21;11(1):10668. doi: 10.1038/s41598-021-90069-x.
Small molecules that contain the (TFMO) moiety were reported to specifically inhibit the class-IIa histone deacetylases (HDACs), an important target in cancer and the disorders of the central nervous system (CNS). However, radiolabeling methods to incorporate the [18F]fluoride into the TFMO moiety are lacking. Herein, we report a novel late-stage incorporation of [18F]fluoride into the TFMO moiety in a single radiochemical step. In this approach the bromodifluoromethyl-1,2,4-oxadiazole was converted into [18F]TFMO via no-carrier-added bromine-[18F]fluoride exchange in a single step, thus producing the PET tracers with acceptable radiochemical yield (3-5%), high radiochemical purity (> 98%) and moderate molar activity of 0.33-0.49 GBq/umol (8.9-13.4 mCi/umol). We validated the utility of the novel radiochemical design by the radiosynthesis of [18F]TMP195, which is a known TFMO containing potent inhibitor of class-IIa HDACs.
含有 (TFMO) 部分的小分子被报道能够特异性抑制 IIa 类组蛋白去乙酰化酶 (HDACs)，这是癌症和中枢神经系统 (CNS) 疾病的重要靶点。然而，将 [18F] 氟化物掺入 TFMO 部分的放射性标记方法尚缺乏。在此，我们报告了一种新的晚期单步放射性化学方法将 [18F] 氟化物掺入 TFMO 部分。在此方法中，通过无载体添加的溴- [18F] 氟化物交换，将溴二氟甲基-1,2,4-噁二唑一步转化为 [18F]TFMO，从而以可接受的放射性化学产率（3-5%）、高放射性化学纯度（>98%）和适中的摩尔活度（0.33-0.49GBq/μmol [8.9-13.4mCi/μmol] 生成 PET 示踪剂。我们通过合成已知的 TFMO 类 IIa HDACs 强效抑制剂 [18F]TMP195 验证了这种新的放射性化学设计的实用性。
