First-in-class -PET radiotracers for GPR39: A platform for noninvasive target engagement imaging in vivo

[18F]GPR39 2.1 enables highly specific PET imaging of GPR39 in vivo, with up to ~90% brain uptake reduction after blockade and 76–90% reductions in knockout mice.

• Why it matters: Lack of suitable GPR39 PET tracers has limited quantitative in vivo study of this zinc-sensing receptor in neurodegeneration and related disorders, slowing target engagement assessment.
• What they did: The authors developed [18F]GPR39 2.1 and evaluated serum stability, in vitro uptake with pharmacological blockade, and in vivo PET plus biodistribution and autoradiography in rats, GPR39 knockout mice, and 5xFAD transgenic mice.
• The result: [18F]GPR39 2.1 showed negligible radiometabolite formation, rapid brain uptake with gradual washout, and disease sensitivity in 5xFAD mice (40% PET and 77% biodistribution reductions), supporting noninvasive GPR39 target engagement imaging.

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