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

Journal Article · Fri Nov 01 04:00:00 EST 1985 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00149a006· OSTI ID:5721893

Tedjamulia, M L; Srivastava, P C; Knapp, Jr, F F

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.

• OSTI ID: 5721893
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 11; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400702* -- Radiochemistry & Nuclear Chemistry-- Properties of Radioactive Materials
550601 -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
BLOOD-BRAIN BARRIER
BODY
BRAIN
CARRIERS
CENTRAL NERVOUS SYSTEM
CHEMICAL PREPARATION
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC USES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIDINES
PYRIDINIUM COMPOUNDS
QUATERNARY COMPOUNDS
RADIOCHEMISTRY
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
RODENTS
SPECIFICITY
SYNTHESIS
USES
VERTEBRATES