School of Biomedical Engineering & Imaging Sciences, Department of Imaging Chemistry & Biology, King's College London, 4th Floor, Lambeth Wing, St. Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK.
National Institute for Health Research Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust & King's College London, 16th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
Future Med Chem. 2020 Mar;12(6):511-521. doi: 10.4155/fmc-2019-0329. Epub 2020 Feb 26.
The receptor for advanced glycation end products (RAGE) is a viable target for early Alzheimer's disease (AD) diagnosis using positron emission tomography (PET) as RAGE overexpression precedes Aβ plaque formation. The development of a carbon-11 analog of FPS-ZM1 (N-benzyl-4-chloro-N-cyclohexylbenzamide, [C]FPS-ZM1), possessing nanomolar affinity for RAGE, may enable the imaging of RAGE for early AD detection. Herein we report an optimized [C]CO-to-[C]CO chemical conversion for the synthesis of [C]FPS-ZM1 and brain autoradiography. The [C]CO-to-[C]CO conversion via C-silanecarboxylate derivatives was achieved with a 57% yield within 30 s from end of [C]CO delivery. [C]FPS-ZM1 was obtained with a decay-corrected isolated radiochemical yield of 9.5%. [C]FPS-ZM1 distribution in brain tissues of wild-type versus transgenic AD model mice showed no statistically significant difference and high nondisplaceable binding.
晚期糖基化终产物受体（RAGE）是使用正电子发射断层扫描（PET）进行早期阿尔茨海默病（AD）诊断的可行靶标，因为 RAGE 的过度表达先于 Aβ斑块形成。FPS-ZM1 的碳-11 类似物（N-苄基-4-氯-N-环己基苯甲酰胺，[C]FPS-ZM1）的开发，对 RAGE 具有纳摩尔亲和力，可能能够对 RAGE 进行成像以用于早期 AD 检测。在此，我们报告了一种优化的 [C]CO 到 [C]CO 化学转化方法，用于合成 [C]FPS-ZM1 和脑放射自显影。通过 C-硅烷羧酸酯衍生物实现了 [C]CO 到 [C]CO 的转化，从 [C]CO 输送结束到转化完成仅需 30 秒，产率为 57%。[C]FPS-ZM1 的衰减校正的分离放射性化学产率为 9.5%。野生型与转基因 AD 模型小鼠脑组织中 [C]FPS-ZM1 的分布没有统计学差异，且无明显可置换结合。
