[123I/125I]-Ro 43-0463, a site specific tracer for MAO-B mapping with autoradiography as well as with SPET

J Recept Signal Transduct Res. 1995 Jan-Mar;15(1-4):581-93. doi: 10.3109/10799899509045241.

Abstract

The compound Ro 43-0463 [N-(2-aminoethyl)-5-iodo-2-pyridinecarboxamide)] is the iodo-analogue of Lazabemid (Ro 19-6327). The latter is well known to bind site specifically with KD = 15.7 nmol/l to the enzyme monoamine oxidase type B (MAO-B) which it inhibits (IC50 = 2 *10(-8) mol/l) time dependently and reversibly. Ro 43-0463 having an IC50 of 3*10(-8) mol/l was labelled with 123I as well as with 125I to get a tool for measuring the MAO-B distribution autoradiographically and in the human brain with SPET (Single Photon Emission Tomography). The halogen exchange reaction of the bromo-precursor (Ro 18-4950) in the presence of CuSO4 and ascorbic acid was applied. The reaction conditions were optimized, varying the parameters time (30 to 105 min), precursor concentration (1 to 3.5 mg) and temperature (130 to 200 degrees C). The purification of [123I/125I]-Ro 43-0463 was performed on HPLC (Lichrosorb RP-18, 5 mu m, 250 x 8 mm) with 0.36 M H3PO4/EtOH 97/3 and 0.01 M (NH4)2HPO4 (1.5 ml/min) as eluent. The labelling yield was found to range between 60 and 70%. The activity concentration ranged between 18.5 and 37 MBq/ml. Autoradiography with rat brain slices was performed using 5 nM [125I]-Ro 43-0463 in TRIS-buffer (pH 7.4) for 90 min at 20 degrees C. It showed a radioactivity pattern corresponding to the known distribution of MAO-B in the rat brain and proved, after displacement with L-Deprenyl (1 mu M), the high specificity of binding Ro 43-0463.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography / methods
  • Brain / diagnostic imaging
  • Brain / enzymology
  • Female
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Kinetics
  • Monoamine Oxidase / classification
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors*
  • Picolinic Acids*
  • Rats
  • Rats, Wistar
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods

Substances

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