Fully Automated Radiosynthesis of [11C]Guanidines for Cardiac PET Imaging,ACS Medicinal Chemistry Letters

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Fully Automated Radiosynthesis of [11C]Guanidines for Cardiac PET Imaging
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2020-10-05 , DOI: 10.1021/acsmedchemlett.0c00479
Austin Y Zhao ₁ , Allen F Brooks ₁ , David M Raffel ₁ , Jenelle Stauff ₁ , Janna Arteaga ₁ , Peter J H Scott _{1,

2} , Xia Shao ₁

Affiliation

Radiolabeled guanidines such as meta-iodobenzylguanidine (MIBG) find utility in nuclear medicine as both diagnostic imaging agents and radiotherapeutics and, over the years, numerous methods for incorporating radionuclides into guanidines have been developed. In connection with a project developing new positron emission tomography (PET) radiotracers for cardiac sympathetic nerve density, we had cause to prepare [¹¹C]3F-PHPOG. However, it quickly became apparent that radiolabeling of guanidine scaffolds with carbon-11 has remained challenging, and historical methods lack compatibility with modern automated radiochemistry synthesis platforms and current Good Manufacturing Practice (cGMP) requirements. To address this challenge, we report a new automated method for radiolabeling guanidines with carbon-11. The method was used to prepare a series of [¹¹C]guanidines in good radiochemical yield (8–76% by radio-HPLC) and was found to have broad substrate scope and tolerance of unprotected OH and NH functional groups. The method was used to synthesize [¹¹C]3F-PHPOG for preclinical imaging, and suitability of the radiotracer for preclinical use was demonstrated through preliminary cardiac PET in New Zealand white rabbits which revealed good cardiac uptake and expected retention in the heart.

中文翻译：

用于心脏 PET 成像的 [11C] 胍的全自动放射合成

放射性标记的胍如间碘苄基胍(MIBG) 在核医学中用作诊断显像剂和放射治疗剂，多年来，已经开发了许多将放射性核素掺入胍中的方法。在开发用于心脏交感神经密度的新型正电子发射断层扫描 (PET) 放射性示踪剂的项目中，我们有理由准备 [ ^11]C]3F-PHPOG。然而，很快就发现用碳 11 对胍支架进行放射性标记仍然具有挑战性，而且历史方法缺乏与现代自动放射化学合成平台和当前良好生产规范 (cGMP) 要求的兼容性。为了应对这一挑战，我们报告了一种用碳 11 对胍进行放射性标记的新自动化方法。该方法用于制备一系列具有良好放射化学产率（放射性 HPLC 为 8-76%）的 [ ¹¹ C] 胍，并发现其具有广泛的底物范围和对未保护的 OH 和 NH 官能团的耐受性。该方法用于合成[ ¹¹C]3F-PHPOG 用于临床前成像，以及放射性示踪剂临床前使用的适用性通过新西兰白兔的初步心脏 PET 得到证明，该 PET 显示良好的心脏摄取和预期的心脏保留。

更新日期：2020-11-12

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