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用于脑部2型大麻素受体PET成像的[F]LU14的研发

Development of [F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain.

作者信息

Teodoro Rodrigo, Gündel Daniel, Deuther-Conrad Winnie, Ueberham Lea, Toussaint Magali, Bormans Guy, Brust Peter, Moldovan Rareş-Petru

机构信息

Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04318 Leipzig, Germany.

Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, BE-3000 Leuven, Belgium.

出版信息

Int J Mol Sci. 2021 Jul 28;22(15):8051. doi: 10.3390/ijms22158051.

DOI:10.3390/ijms22158051
PMID:34360817
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8347709/
Abstract

Cannabinoid receptors type 2 (CB2R) represent an attractive therapeutic target for neurodegenerative diseases and cancer. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor receptor density and/or occupancy during a CB2R-tailored therapy, we herein describe the radiosynthesis of -[F]1-(4-fluorobutyl--((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([F]) starting from the corresponding mesylate precursor. The first biological evaluation revealed that [F] is a highly affine CB2R radioligand with >80% intact tracer in the brain at 30 min p.i. Its further evaluation by PET in a well-established rat model of CB2R overexpression demonstrated its ability to selectively image the CB2R in the brain and its potential as a tracer to further investigate disease-related changes in CB2R expression.

摘要

2型大麻素受体（CB2R）是神经退行性疾病和癌症颇具吸引力的治疗靶点。为了开发一种正电子发射断层扫描（PET）放射性示踪剂，以在CB2R定制治疗期间监测受体密度和/或占有率，我们在此描述了从相应的甲磺酸盐前体开始的 -[F]1-(4-氟丁基--((1s,4s)-4-甲基环己基)-2-氧代-1,2-二氢-1,8-萘啶-3-甲酰胺（[F]）的放射性合成。首次生物学评估表明，[F]是一种高亲和力的CB2R放射性配体，注射后30分钟时脑内完整示踪剂含量>80%。在成熟的CB2R过表达大鼠模型中通过PET对其进行的进一步评估表明，它有能力在脑内选择性地成像CB2R，并且有潜力作为一种示踪剂来进一步研究与疾病相关的CB2R表达变化。

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