Synthesis and evaluation of 5-HT3 receptor antagonist [11C]KF17643.
For imaging CNS 5-HT3 receptors by PET, a high affinity 5-HT3 receptor ligand, endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 2-(n-propyloxy)-4-quinolinecarboxylate (KF17643), have been labeled with 11C. N-Methylation of the desmethyl compound with [11C]methyl iodide followed by HPLC separation produced [11C]KF17643 with the decay-corrected radiochemical yield of 19-28%, the specific activity of 7.5-49 GBq/mumol and the radiochemical purity of > 99% at 35-40 min from EOB. After i.v. injection of [11C]KF17643 into mice, it was taken by the brain at a high level and was stable for metabolism, but no sign for the 5-HT3 receptor selectivity was found in the brain tissues by the tissue sampling and autoradiography, probably because of large non-specific binding. The [11C]KF17643 was not suitable as a PET ligand for mapping the CNS 5-HT3 receptors.
Ishiwata
K
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
Saito
N
N
Yanagawa
K
K
Furuta
R
R
Ishii
S
S
Kiyosawa
M
M
Homma
Y
Y
Ishii
K
K
Suzuki
F
F
Senda
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006847:Hydrocarbons, Iodinated; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011804:Quinolines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011985:Receptors, Serotonin / Q000032:analysis* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014326:Tropanes / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D006847:Hydrocarbons, Iodinated; D007202:Indicators and Reagents; D011804:Quinolines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D014326:Tropanes; C102271:KF 17643; C014055:methyl iodide