Details

Autor(en) / Beteiligte

• Yuan, Gengyang
• Dhaynaut, Maeva
• Guehl, Nicolas J.
• Afshar, Sepideh
• Huynh, Dalena
• Moon, Sung-Hyun
• Iyengar, Suhasini M.
• Jain, Manish Kumar
• Pickett, Julie E.
• Kang, Hye Jin
• Ondrechen, Mary Jo
• El Fakhri, Georges
• Normandin, Marc D.
• Brownell, Anna-Liisa

Titel

Design, Synthesis, and Characterization of [18F]mG2P026 as a High-Contrast PET Imaging Ligand for Metabotropic Glutamate Receptor 2

Ist Teil von

• Journal of medicinal chemistry, 2022-07, Vol.65 (14), p.9939-9954

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• An array of triazolopyridines based on JNJ-46356479 (6) were synthesized as potential positron emission tomography radiotracers for metabotropic glutamate receptor 2 (mGluR2). The selected candidates 8–10 featured enhanced positive allosteric modulator (PAM) activity (20-fold max.) and mGluR2 agonist activity (25-fold max.) compared to compound 6 in the cAMP GloSensor assays. Radiolabeling of compounds 8 and 9 (mG2P026) was achieved via Cu-mediated radiofluorination with satisfactory radiochemical yield, >5% (non-decay-corrected); high molar activity, >180 GBq/μmol; and excellent radiochemical purity, >98%. Preliminary characterization of [18F]8 and [18F]9 in rats confirmed their excellent brain permeability and binding kinetics. Further evaluation of [18F]9 in a non-human primate confirmed its superior brain heterogeneity in mapping mGluR2 and higher affinity than [18F]6. Pretreatment with different classes of PAMs in rats and a primate led to similarly enhanced brain uptake of [18F]9. As a selective ligand, [18F]9 has the potential to be developed for translational studies.