Synthesis of 5-HT3 receptor antagonists, [11C]Y-25130 and [11C]YM060.
Two high-affinity 5-HT3 receptor ligands, Y-25130 and YM 060, have been labeled with 11C for use in PET studies to measure 5-HT3 receptors. The [11C]Y-25130 was prepared by N-methylation of nor-Y-25130-BH3 complex with [11C]CH3I in the presence of K2CO3 followed by HCl hydrolysis. Likewise, N-methylation of nor-YM060 gave [11C]YM060. After HPLC separation, the decay-corrected radiochemical yield of the two 11C-labeled ligands was 34-40% based on [11C]CH3I, the specific activity was 10-12 GBq/mumol at 35-40 min from EOB, and the radiochemical and chemical purities were > 99%. In mice, the brain uptake of the two compounds was the lowest among the tissues investigated, but the level of the brain radioactivity increased with time.
Ishiwata
K
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
Ishii
K
K
Ishii
S
S
Senda
M
M
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D014018:Tissue Distribution
D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002250:Carbon Radioisotopes; D010078:Oxazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C070671:azasetron; C071315:ramosetron