title: Evaluation of the brain-specific delivery of radioiodinated (iodophenyl)alkyl-substituted amines coupled to a dihydropyridine carrier.
abstract: To evaluate the potential usefulness of radioiodinated phenylamines attached to dihydropyridine carriers as a means of brain-specific delivery of radiopharmaceuticals, 1-methyl-3-[N-[beta- (4-[125I]iodophenyl)ethyl]carbamoyl]-1,4-dihydropyridine ([125I]-9) and 1-methyl-3-[N-(4-[125I]iodophenyl)carbamoyl]-1,4-dihydropyridine ([125I]-13) have been prepared by dithionite reduction of the corresponding pyridinium precursors, [125I]-8 and [125I]-12, respectively. Formation of 8 involved coupling of (p-aminophenyl)ethylamine with N-succinimidyl (1-methyl-3-pyridinio)formate iodide (4) followed by transformation to the corresponding N-piperidinyl- (6) or (diethylamino)- (7) triazines that were converted to 8 by treatment with HI. Alternatively, 12 was prepared by initial conversion of (4-amino-phenyl)mercuric acetate (10) to 4-iodoaniline (11) by treatment with I2 and then coupling with 4. The radioiodinated quaternary products, 8 and 12, showed low brain uptake and low brain to blood ratios, whereas the dihydropyridine analogues, 9 and 13, showed comparatively good brain uptake and good brain to blood ratios in rats. These data demonstrate that dihydropyridine-coupled radiopharmaceuticals can cross the blood-brain barrier and the technique may be useful for the measurement of cerebral blood perfusion.
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D004095:Dihydropyridines; D005260:Female; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000097:blood / Q000138:chemical synthesis / Q000378:metabolism*; D011725:Pyridines / Q000097:blood / Q000138:chemical synthesis / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000097:blood / Q000138:chemical synthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004095:Dihydropyridines; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D011725:Pyridines; D011726:Pyridinium Compounds; C047226:1-methyl-3-(N (4-iodophenylethyl)carbamoyl)pyridinium; C047227:1-methyl-3-(N-(4-iodophenylethyl)carbamoyl)-1,4-dihydropyridine; C047228:1-methyl-3-(N-(4-iodophenyl)carbamoyl)pyridinium iodide; C047229:1-methyl-3-(N-(4-iodophenyl)carbamoyl)-1,4-dihydropyridine