Work

Selective Mu-Opioid Receptor Imaging Using 18F-Labeled Carfentanils

Year: 2025

Type: article

Abstract: Carfentanil, a highly potent synthetic opioid, paradoxically serves as a crucial positron emission tomography (PET) imaging tool in neurobiological studies of the mu-opioid receptor (MOR) system when labeled with carbon-11 ([ 11 C]CFN). However, its clinical research use is hindered by extreme potency and the limited availability of short-lived carbon-11 ( t 1/2 = 20.4 min). We present fluorine-18-labeled fluorocarfentanils ([ 18 F]FCFNs), which can be produced at higher molar activity, allowing for lower mass doses and benefiting from the longer half-life of fluorine-18 ( t 1/2 = 109.8 min), facilitating broader accessibility. Using copper-mediated radiofluorination, we synthesized a small [ 18 F]FCFN library and conducted preclinical imaging evaluations. Two candidates, o - 18 F-1 and p - 18 F-2, showed optimal brain uptake, favorable pharmacokinetics, and high MOR-specific binding. Selectivity was confirmed through in vitro binding assays and in vivo PET scans. These [ 18 F]FCFNs are promising for accessible human brain MOR imaging.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/acs.jmedchem.4c02287