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

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 ([¹¹C]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 ([¹⁸F]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 [¹⁸F]FCFN library and conducted preclinical imaging evaluations. Two candidates, o-¹⁸F-1 and p-¹⁸F-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 [¹⁸F]FCFNs are promising for accessible human brain MOR imaging.