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

Area of Science:

• Neuroscience
• Radiochemistry
• Pharmacology

Background:

• Carfentanil labeled with carbon-11 ([11C]CFN) is a positron emission tomography (PET) tracer for mu-opioid receptor (MOR) research.
• Its clinical utility is limited by high potency and the short half-life of carbon-11 (20.4 min).

Purpose of the Study:

• To develop novel fluorine-18 labeled fluorocarfentanils ([18F]FCFNs) for improved brain MOR imaging.
• To overcome the limitations of [11C]CFN regarding accessibility and dose.

Main Methods:

• Synthesis of an [18F]FCFN library using copper-mediated radiofluorination.
• Preclinical evaluation including in vitro binding assays and in vivo PET imaging in animal models.
• Assessment of brain uptake, pharmacokinetics, and MOR-specific binding.

Main Results:

• Two [18F]FCFN candidates demonstrated optimal brain uptake and favorable pharmacokinetics.
• High MOR-specific binding and selectivity were confirmed.
• The longer half-life of fluorine-18 (109.8 min) allows for broader accessibility.

Conclusions:

• The developed [18F]FCFNs are promising PET tracers for accessible human brain MOR imaging.
• These novel tracers offer advantages over existing [11C]CFN agents.
• Facilitates wider research into the MOR system.