Iododerivative of pargyline: a potential tracer for the exploration of monoamine oxidase sites by SPECT.
Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [125I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [125I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [125I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with 123I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.
Laboratoire de Biophysique Médicale et Pharmaceutique, INSERM U316, Tours-France.
I
I
Lena
J E
JE
Ombetta
S
S
Chalon
A M
AM
Dognon
J L
JL
Baulieu
Y
Y
Frangin
L
L
Garreau
J C
JC
Besnard
D
D
Guilloteau
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D008995:Monoamine Oxidase / Q000032:analysis*; D009928:Organ Specificity; D010293:Pargyline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010870:Pineal Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
C097432:2-iodopargyline; D007457:Iodine Radioisotopes; D010293:Pargyline; D008995:Monoamine Oxidase