Regional brain uptake of the muscarinic ligand, [ 18F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice

• Published in: Neuropharmacology 2003-04, Vol.44 (5), p.653-661
• Main Authors: Jagoda, E.M., Kiesewetter, D.O., Shimoji, K., Ravasi, L., Yamada, M., Gomeza, J., Wess, J., Eckelman, W.C.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain - metabolism; Cerebral blood flow; Female; Fluorine Radioisotopes - metabolism; KO mice; Ligands; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscarinic receptors; Pyridines - metabolism; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptor, Muscarinic M4; Receptors, Muscarinic - deficiency; Receptors, Muscarinic - genetics; Saturability; Thiazoles - metabolism
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(03)00050-9

A muscarinic receptor radioligand, 3-(3-(3-fluoropropyl)thio) -1,2,5,thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (fP-TZTP) radiolabeled with the positron emitting radionuclide 18F ([ 18F]FP-TZTP) displayed regional brain distribution consistent with M2 receptor densities in rat brain. The purpose of the present study is to further elucidate the subtype selectivity of [ 18F]FP-TZTP using genetically engineered mice which lacked functional M1, M2, M3, or M4 muscarinic receptors. Using ex vivo autoradiography, the regional brain localization of [ 18F]FP-TZTP in M2 knockout (M2 KO) was significantly decreased (51.3 to 61.4%; P