Fluorine-18 Radiolabeled Single-Chain Antibody Variable Fragment 1F4 Targets α1-Subunit Gamma-Aminobutyric Acid Type A Receptors in Mice - UTU Research Portal

A1 Refereed original research article in a scientific journal

Fluorine-18 Radiolabeled Single-Chain Antibody Variable Fragment 1F4 Targets α1-Subunit Gamma-Aminobutyric Acid Type A Receptors in Mice

Authors: García de Lucas, Ángel; Samani, Negar A.; Moisio, Olli; Kovacs, Luciana; Savela, Risto; Soini, Sanna L.; Oksanen, Sami; Helin, Jatta S.; Rajander, Johan; Airaksinen, Anu J.; Lamminmäki, Urpo; López-Picón, Francisco

Publisher: American Chemical Society (ACS)

Publication year: 2026

Journal: Journal of Medicinal Chemistry

ISSN: 0022-2623

eISSN: 1520-4804

DOI: https://doi.org/10.1021/acs.jmedchem.5c02984

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Partially Open Access publication channel

Web address : https://doi.org/10.1021/acs.jmedchem.5c02984

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/515596471

Self-archived copy's licence: CC BY

Self-archived copy's version: Publisher`s PDF

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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Funding information in the publication:
This work was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie (grant 891455) as well as by the Research Council of Finland’s project (#343608) and InFLAMES
Flagship (337530/357910).