Čolović Milena, Rousseau Etienne, Zhang Zhengxing, Lau Joseph, Zhang Chengcheng, Kuo Hsiou-Ting, Yang Hua, Schaffer Paul, Lin Kuo-Shyan
Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
Life Sciences, TRIUMF, Vancouver, BC V6T 2A3, Canada.
Bioorg Med Chem Lett. 2018 Dec 1;28(22):3579-3584. doi: 10.1016/j.bmcl.2018.06.014. Epub 2018 Jun 8.
In this study, we synthesized F-ASu-BF, a close boramino acid analog of 5-[F]fluoro-aminosuberic acid (F-ASu), via F-F isotope exchange reaction and evaluated its potential for imaging with positron emission tomography (PET). F-ASu-BF was stable in mouse plasma and taken up into PC3 prostate cancer cells via the system x amino acid transporter. The continuous use of isoflurane for anesthesia during dynamic imaging acquisition slowed down the excretion of F-ASu-BF and enabled visualization of PC3 tumor xenografts in mice. In contrast, no tumor visualization was observed from static images of F-BF-ASu due to its rapid renal excretion mediated in part by the organic anion transporter. Our data indicate that the pharmacokinetics of amino acids could be altered after being converted into their boramino acid analogs. Therefore, care should be taken when using the boramino acid strategy to design and prepare F-labeled tracers for imaging amino acid transporters/receptors with PET.
在本研究中，我们通过F-F同位素交换反应合成了F-ASu-BF，它是5-[F]氟亚氨基辛二酸（F-ASu）的一种紧密硼氨基类似物，并评估了其正电子发射断层扫描（PET）成像的潜力。F-ASu-BF在小鼠血浆中稳定，并通过系统x氨基酸转运体被摄取到PC3前列腺癌细胞中。在动态成像采集过程中持续使用异氟烷进行麻醉减缓了F-ASu-BF的排泄，并使小鼠体内的PC3肿瘤异种移植能够可视化。相比之下，由于F-BF-ASu的快速肾排泄（部分由有机阴离子转运体介导），其静态图像中未观察到肿瘤可视化。我们的数据表明，氨基酸转化为其硼氨基类似物后，其药代动力学可能会发生改变。因此，在使用硼氨基酸策略设计和制备用于PET成像氨基酸转运体/受体的F标记示踪剂时应谨慎。
