Evaluation of radioiodinated iodoclorgyline as a SPECT radiopharmaceutical for MAO-A in the brain.
An in vivo estimation of the newly synthesized MAO-A specific inhibitor, [125I]-labeled N-[3(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2- propynylamine ([125I]-iodoclorgyline), was performed. Retention of the radioactivity of this radioligand was observed in the brain from 1 h post-injection. Pretreatments with clorgyline and l-deprenyl showed selective binding of [125I]-iodoclorgyline to MAO-A in the brain at 24 h post-injection. Moreover, a good correlation (r = 0.907) between the uptake of [125I]-iodoclorgyline and MAO-A enzyme activity in the cortex was observed in the pretreatment study with several doses of clorgyline. Although improvement to increase the brain/blood ratio is desirable because of slow blood clearance of the radioactivity, radioiodinated iodoclorgyline may serve as a useful SPECT radiopharmaceutical for quantitative analysis of MAO-A in the brain.
Hirata
M
M
Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Magata
Y
Y
Ohmomo
Y
Y
Saji
H
H
Murakami
K
K
Takagaki
T
T
Yamamura
N
N
Tanaka
C
C
Konishi
J
J
Yokoyama
A
A
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003010:Clorgyline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000378:metabolism* / Q000493:pharmacokinetics; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism; D008995:Monoamine Oxidase / Q000032:analysis / Q000378:metabolism*; D011869:Radioligand Assay / Q000379:methods; D012642:Selegiline / Q000494:pharmacology; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D007457:Iodine Radioisotopes; D007527:Isoenzymes; C074503:6-iodoclorgyline; D012642:Selegiline; D008995:Monoamine Oxidase; D003010:Clorgyline