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Updated: Feb 11, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Fluorine-18 Radiolabeled Single-Chain Antibody Variable Fragment 1F4 Targets α1-Subunit Gamma-Aminobutyric Acid Type
Ángel García de Lucas1,2,3, Negar A Samani1,4, Olli Moisio1,4
1Turku PET Centre, University of Turku and Turku University Hospital, FI-20520 Turku, Finland.
Abstract:
Gamma-aminobutyric acid type A (GABA-A) receptors are the principal inhibitory neurotransmitter receptors in the central nervous system (CNS), but their functions in the peripheral nervous system (PNS) and organs such as the heart remain poorly understood. These receptors comprise various subtypes based on subunit composition with differential brain and heart expression linked to distinct pathologies. Current positron emission tomography (PET) imaging protocols use radioligands lacking subtype specificity. To address this, we developed a PET tracer targeting the α1 subunit. The α1-specific single-chain variable fragment (scFv) 1F4 was engineered from the variable domains of monoclonal antibody (mAb) 1F4. It was efficiently 18F-labeled under mild conditions via biorthogonal inverse electron demand Diels-Alder (iEDDA) ligation. PET biodistribution in mice showed favorable pharmacokinetics for [18F]F-Tz-TCO-scFv 1F4 with specific α1 subunit binding in the brain, heart, and lungs. This tracer promises to evaluate GABA-A α1 distribution and expression in peripheral organs, particularly the heart.
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