Pargyline‐Sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia

Abstract

The distribution of radioiodinated N-methyl-4-(4-hydroxy-3-iodobenzyl)-1,2,3,6-tetrahydropyridine (MHTP), an analog of the reportedly nontoxic N-methyl-4-benzyl-1,2,3,6-tetrahydropyridine, (4-homo-MPTP), has been studied in the primate. [123I]MHTP-derived radioactivity exhibited a progressive accumulation and prolonged retention within the primate eye. Following iv injection, [123I]MHTP rapidly accumulated within the primate brain and was subsequently oxidized to a radiolabeled metabolite. The half-life of [123I]MHTP-derived radioactivity within the primate brain was 50 min. The highest concentrations of radioactivity were found in the caudate-putamen and the frontal, temporal and cingulate cortices; the substantia nigra and inferior olivary nucleus were labeled with medium intensity. Very low concentrations of radiolabel were detected in the cerebellum and white matter. Selective accumulation of [125I]MHTP-derived radioactivity within these structures was blocked by pretreatment with pargyline, suggesting that monoamine oxidase B is involved in the bioactivation of radioiodinated MHTP.

Effects of Mitochondrial Toxins on the Brain Amino Acid Concentrations

“…Radiolabelling studies demonstrated that the highest concentrations of radioactivity following the intravenous injection of a radiolabelled MPTP analogue were found in the caudate-putamen and the frontal, temporal and cingulate cortices; the substantia nigra and inferior olivary nucleus were labelled with medium intensity. Only very low concentrations of the radiolabelled analogue were detected in the cerebellum and white matter (12).…”

In Vivo Metabolic Trapping Radiotracers for Imaging Monoamine Oxidase-A and -B Enzymatic Activity

“…The syntheses of radiolabeled forms of N , N -dimethylphenylethylamine were reported, initial biodistribution studies were reported in rodents, and even a single human PET image was presented . Preliminary studies in both rat and primate were also done with carbon-11-labeled MPTP and a radioiodinated tetrahydropyridine ( N -methyl-4-(4′-hydroxy-3′-[ 125 I]­iodophenyl)-1,2,3,6-tetrahydropyridine), but no additional reports were made for use of either compound. Further development and validation (demonstration of isoform selectivity, pharmacokinetic analyses) of noncovalent metabolic trapping radiotracers for MAO have not been pursued, and there have been no applications of this concept to studies of MAO in human diseases.…”