Details

Autor(en) / Beteiligte

• Fujinaga, Masayuki
• Yamasaki, Tomoteru
• Yui, Joji
• Hatori, Akiko
• Xie, Lin
• Kawamura, Kazunori
• Asagawa, Chiharu
• Kumata, Katsushi
• Yoshida, Yuichiro
• Ogawa, Masanao
• Nengaki, Nobuki
• Fukumura, Toshimitsu
• Zhang, Ming-Rong

Titel

Synthesis and Evaluation of Novel Radioligands for Positron Emission Tomography Imaging of Metabotropic Glutamate Receptor Subtype 1 (mGluR1) in Rodent Brain

Ist Teil von

• Journal of medicinal chemistry, 2012-03, Vol.55 (5), p.2342-2352

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• We designed three novel positron emission tomography ligands, N-(4-(6-(isopropylamino)­pyrimidin-4-yl)-1,3-thiazol-2-yl)-4-[11C]­methoxy-N-methylbenzamide ([11C]6), 4-[18F]­fluoroethoxy-N-[4-[6-(isopropylamino)­pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([18F]7), and 4-[18F]­fluoropropoxy-N-[4-[6-(isopropylamino)­pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([18F]8), for imaging metabotropic glutamate receptor type 1 (mGluR1) in rodent brain. Unlabeled compound 6 was synthesized by benzoylation of 4-pyrimidinyl-2-methylaminothiazole 10, followed by reaction with isopropylamine. Removal of the methyl group in 6 gave phenol precursor 12 for radiosynthesis. Two fluoroalkoxy analogues 7 and 8 were prepared by reacting 12 with tosylates 13 and 14. Radioligands [11C]6, [18F]7, and [18F]8 were synthesized by O-[11C]­methylation or [18F]­fluoroalkylation of 12. Compound 6 showed high in vitro binding affinity for mGluR1, whereas 7 and 8 had weak affinity. Autoradiography using rat brain sections showed that [11C]6 binding is aligned with the reported distribution of mGluR1 with high specific binding in the cerebellum and thalamus. PET study with [11C]6 in rats showed high brain uptake and a similar distribution pattern to that in autoradiography, indicating the usefulness of [11C]6 for imaging brain mGluR1.