Evaluation of the brain-specific delivery of radioiodinated (iodophenyl)alkyl-substituted amines coupled to a dihydropyridine carrier

Article abstract of DOI:10.1021/jm00149a006

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-[β-(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- or (diethylamino)- triazines that were converted to 8 by treatment with HI. Alternatively, 12 was prepared by initial conversion of (4-aminophenyl)mercuric acetate to 4-iodoaniline 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.