Flubatine

Flubatine ([18F]-norchloro-fluoro-homoepibatidine) is a fluorine-18 (¹⁸F) labeled radiotracer and radioligand for positron emission tomography (PET) imaging, developed as a high-affinity ligand for brain nicotinic acetylcholine receptors (nAChRs) of the α4β2 subtype. It is used to image cholinergic deficits in disorders such as Alzheimer’s disease and Parkinson’s disease. Both (+)- and (−)- enantiomer bind specifically to α4β2 nAChRs.

Synthesis

Flubatine is prepared by radiolabeling a precursor molecule with fluorine-18 under no-carrier-added conditions. The synthetic route involves two main steps:

• Precursor synthesis: Optically pure precursor compounds (one for each enantiomer) are synthesized by organic chemical methods starting from epibatidine-like intermediates.
• Radiolabeling: The [¹⁸F]fluoride ion is introduced by nucleophilic aromatic substitution of the precursor under controlled conditions (often using cryptand-assisted [¹⁸F]fluoride and heat). Using a trimethylammonium leaving group on the pyridine ring allows for efficient fluorination.

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