Biodistribution and estimated radiation burden for a new 123I-labelled monoamine oxidase-B inhibitor, Ro 43-0463: a preliminary report

J Nucl Biol Med (1991). 1994 Dec;38(4 Suppl 1):59-62.

Abstract

The selective, reversible inhibitor of monoamine oxidase B (MAO-B), Ro 19-6327 (Lazabamide) N-aminoethyl-5-chloro-picolinamide, inhibits the enzyme with an initial competitive phase, followed by a time-dependent inhibition of MAO-B; i.e. Ro 19-6327 is a substrate for MAO-B, and after its oxidation it is activated into an intermediate form which remains tightly bound to the enzyme's active site. Our radiopharmaceutical is a new 123I-labelled derivative of Ro 19-6327, N-aminoethyl-5-[123I]iodo-picolinamide, which seems to be a potentially useful SPECT tracer for the imaging of the MAO-B enzyme distributions. The first biodistribution of this compound was measured in rats at 6 different points in time (10, 25, 40, 60, 180 and 900 minutes post-injection). For each point the average from three animals was taken. In the brain there was an activity plateau over the first hour. In the first hour post-injection the brain-to-blood ratio was over 1, with a maximum ratio of 1.24 at 25 minutes post-injection. Because MAO-B is abundant in the ependyma, pineal and cerebellar Bergmann glia cells, this ratio of 1.24 over the whole brain is encouraging. At first, radioactivity was principally and rapidly accumulated in the liver. After 1 hour, about 37% of the injected activity is accumulated there. The elimination of the compound seemed to take place mainly through the hepatobiliary system (about 75%), but also via the kidneys (about 25%). Fifteen hours post-injection, only 4% (corrected for decay) of the injected radioactivity was left in the body.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Body Burden
  • Female
  • Humans
  • Iodine Radioisotopes*
  • Monoamine Oxidase Inhibitors*
  • Picolinic Acids*
  • Radiation Dosage
  • Rats
  • Rats, Wistar
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Iodine Radioisotopes
  • Monoamine Oxidase Inhibitors
  • Picolinic Acids
  • N-(2-aminoethyl)-5-iodo-2-pyridinecarboxamide