Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Jülich GmbH , Jülich 52428, Germany.
Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne , Cologne 50937, Germany.
J Med Chem. 2018 Jan 11;61(1):189-206. doi: 10.1021/acs.jmedchem.7b01245. Epub 2017 Nov 13.
Tryptophan and its metabolites are involved in different physiological and pathophysiological processes. Consequently, positron emission tomography (PET) tracers addressing tryptophan metabolic pathways should allow the detection of different pathologies like neurological disorders and cancer. Herein we report an efficient method for the preparation of fluorotryptophans labeled in different positions with F and their biological evaluation. 4-7-[F]Fluorotryptophans ([F]FTrps) were prepared according to a modified protocol of alcohol-enhanced Cu-mediated radiofluorination in 30-53% radiochemical yields. In vitro experiments demonstrated high cellular uptake of 4-7-[F]FTrps in different tumor cell lines. 4, 5-, and 6-[F]FTrps, although stable in vitro, suffered from rapid in vivo defluorination. In contrast, 7-[F]FTrp demonstrated a high in vivo stability and enabled a clear delineation of serotonergic areas and melatonin-producing pineal gland in rat brains. Moreover 7-[F]FTrp accumulated in different tumor xenografts in a chick embryo CAM model. Thus, 7-[F]FTrp represents a highly promising PET probe for imaging of Trp metabolism.
色氨酸及其代谢物参与不同的生理和病理生理过程。因此，针对色氨酸代谢途径的正电子发射断层扫描（PET）示踪剂应该能够检测到不同的疾病，如神经紊乱和癌症。本文报道了一种高效的方法，用于制备在不同位置用 F 标记的氟代色氨酸及其生物学评价。根据改进的醇增强 Cu 介导放射性氟代方案，以 30-53%的放射化学产率制备了 4-7-[F]氟代色氨酸([F]FTrps)。体外实验表明，不同肿瘤细胞系中 4-7-[F]FTrps 的细胞摄取率很高。尽管 4、5-和 6-[F]FTrps 在体外稳定，但在体内迅速脱氟。相比之下，7-[F]FTrp 在体内表现出很高的稳定性，并能够清晰地区分大鼠大脑中的 5-羟色胺能区域和产生褪黑素的松果体。此外，7-[F]FTrp 在鸡胚 CAM 模型中的不同肿瘤异种移植中积累。因此，7-[F]FTrp 是一种很有前途的 PET 探针，可用于成像色氨酸代谢。
