ABSTRACT
The novel quinoline-2-carboxamide derivatives N-[methyl-11C]-3-methyl-4-phenyl-N-(phenylmethyl)quinoline-2-carboxamide ([11C]4), (+/-)-N-[methyl-11C]-3-methyl-N-(1-methylpropyl)-4-phenylquinoline-2-carboxamide ([11C]5), and (+/-)-N-[methyl-11C]-3-methyl-4-(2-fluorophenyl)-N-(1-methylpropyl)quinoline-2-carboxamide ([11C]6) were labeled with carbon-11 (t1/2 = 20.4 min, beta+ = 99.8%) as potential radioligands for the noninvasive assessment of peripheral benzodiazepine type receptors (PBR) in vivo with positron emission tomography (PET). The radiosynthesis consisted of N-methylation of the desmethyl precursors 3-methyl-4-phenyl-N-(phenylmethyl)quinoline-2-carboxamide (4a), (+/-)-3-methyl-N-(1-methylpropyl)-4-phenylquinoline-2-carboxamide (5a), and (+/-)-4-(2-fluorophenyl)-3-methyl-N-(1-methylpropyl)quinoline-2-carboxamide (6a) with either [11C]methyl iodide or [11C]methyl triflate in the presence of tetrabutylammonium hydroxide or potassium hydroxide in dimethylformamide. The radioligands [11C]4, [11C]5, and [11C]6 were synthesized with over 99% radiochemical purity in 30 min, 30 +/- 5% radiochemical yield, calculated at the end of synthesis (EOS) non-decay-corrected, and 2.5 +/- 1.2 Ci/micromol of specific radioactivity. Inhibition studies in rats following intravenous pre-administration of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195, 1) showed high specific binding to PBR of [11C]4, [11C]5, and [11C]6 in heart, lung, kidney, adrenal gland, spleen, and brain. The biological data suggest that [11C]5, [11C]6, and particularly [11C]4 are promising radioligands for PBR imaging in vivo with PET.
Subject(s)
Amides/chemical synthesis , Quinolines/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Receptors, GABA-A/metabolism , Amides/chemistry , Amides/metabolism , Animals , Carbon Radioisotopes , Isotope Labeling , Ligands , Male , Methylation , Quinolines/chemistry , Quinolines/metabolism , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/metabolism , Rats , Tissue Distribution , Tomography, Emission-ComputedABSTRACT
In the present experimental study the author estimates that within the general structures of the personality of intellectually handicapped there are some fundamental ones around them, which give the direction of the development of harmonious or disharmonious personality, all the other characteristics that are obviously manifest in the handicapped patients' behaviour are polarized.
