Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94158, United States.
UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94158, United States.
ACS Sens. 2023 Dec 22;8(12):4554-4565. doi: 10.1021/acssensors.3c01477. Epub 2023 Nov 22.
Imaging infections in patients is challenging using conventional methods, motivating the development of positron emission tomography (PET) radiotracers targeting bacteria-specific metabolic pathways. Numerous techniques have focused on the bacterial cell wall, although peptidoglycan-targeted PET tracers have been generally limited to the short-lived carbon-11 radioisotope ( = 20.4 min). In this article, we developed and tested new tools for infection imaging using an amino sugar component of peptidoglycan, namely, derivatives of -acetyl muramic acid (NAM) labeled with the longer-lived fluorine-18 ( = 109.6 min) radioisotope. Muramic acid was reacted directly with 4-nitrophenyl 2-[F]fluoropropionate ([F]NFP) to afford the enantiomeric NAM derivatives ()-[F]FMA and ()-[F]FMA. Both diastereomers were easily isolated and showed robust accumulation by human pathogens in vitro and in vivo, including . These results form the basis for future clinical studies using fluorine-18-labeled NAM-derived PET radiotracers.
使用常规方法对患者体内的感染进行成像具有挑战性，这促使人们开发了针对细菌特定代谢途径的正电子发射断层扫描 (PET) 放射性示踪剂。许多技术都集中在细菌细胞壁上，尽管针对肽聚糖的 PET 示踪剂通常仅限于短寿命的碳-11 放射性同位素（ = 20.4 分钟）。在本文中，我们开发并测试了使用肽聚糖的氨基糖成分，即带有长寿命氟-18（ = 109.6 分钟）放射性同位素标记的 -乙酰基 muramic 酸 (NAM) 的衍生物，用于感染成像的新工具。Muramic 酸与 4-硝基苯基 2-[F]氟丙酸酯 ([F]NFP) 直接反应，得到对映体 NAM 衍生物 ()-[F]FMA 和 ()-[F]FMA。两种非对映异构体都很容易分离，并在体外和体内显示出人类病原体的强烈积累，包括。这些结果为未来使用氟-18 标记的 NAM 衍生 PET 放射性示踪剂进行临床研究奠定了基础。
