Abstract：
Organotrifluoroborates have gained acceptance as radioprosthetic groups for radiofluorination. Of these, the zwitterionic prosthetic group \"AMBF3 \" with a quaternary dimethylammonium ion dominates the trifluoroborate space. Herein, we report on imidazolium-methylene trifluoroborate (ImMBF3 ) as an alternative radioprosthetic group and report on its properties in the context of a PSMA-targeting EUK ligand that was previously been conjugated to AMBF3 . The ImMBF3 is readily synthesized from imidazole and conjugated via CuAAC \"click\" chemistry to give a structure similar to PSMA-617. 18 F-labeling proceeded in one step per our previous reports and imaged in LNCaP-xenograft bearing mice. The [18 F]-PSMA-617-ImMBF3 tracer proved to be less polar (LogP7.4 = -2.95 ± 0.03) while showing a significantly lower solvolytic rate (t1/2 = 8100 min) and slightly higher molar activity (Am) at 174 ± 38 GBq/μmol. Tumor uptake was measured at 13.7 ± 4.8%ID/g and a tumor:muscle ratio of 74.2 ± 35.0, tumor:blood ratio of 21.4 ± 7.0, tumor:kidney ratio of 0.29 ± 0.14, and tumor:bone ratio of 23.5 ± 9.5. In comparison with previously reported PSMA-targeting EUK-AMBF3 conjugates, we have altered the LogP7.4 value, tuned the solvolytic half-life of the prosthetic, and increased radiochemical conversion while achieving similar tumor uptake, contrast ratios, and molar activities compared with AMBF3 bioconjugates.
摘要：
有机三氟硼酸酯已被接受为用于放射性氟化的放射性假体基团。其中,具有季二甲基铵离子的两性离子辅基“AMBF3”在三氟硼酸盐空间中占主导地位。在这里，我们报道了咪唑-亚甲基三氟硼酸酯（ImMBF3）作为替代的放射性假体基团，并报道了其在以前与AMBF3缀合的PSMA靶向EUK配体的情况下的性质。ImMBF3很容易由咪唑合成，并通过CuAAC“点击”化学进行共轭，得到类似于PSMA-617的结构。18根据我们先前的报告，F标记在一个步骤中进行，并在带有LNCaP异种移植物的小鼠中成像。[18F]-PSMA-617-ImMBF3示踪剂被证明极性较小（LogP7.4=-2.95±0.03），同时显示出较低的溶剂分解速率（t1/2=8100分钟）和稍高的摩尔活性（Am）在174±38GBq/μmol。测得的肿瘤摄取为13.7±4.8％ID/g，肿瘤：肌肉比为74.2±35.0，肿瘤：血液比为21.4±7.0，肿瘤：肾脏比为0.29±0.14，肿瘤：骨骼比为23.5±9.5。与先前报道的PSMA靶向EUK-AMBF3缀合物相比，我们更改了LogP7.4值，调整了假肢的溶解半衰期，增加放射化学转化，同时实现类似的肿瘤摄取，对比度,和与AMBF3生物缀合物相比的摩尔活性。
