IODODERIVATIVE OF PARGYLINE - A POTENTIAL TRACER FOR THE EXPLORATION OF MONOAMINE-OXIDASE SITES BY SPECT

Monoamine oxidases are important in the regulation of monoaminergic ne urotransmission. An increase in monoamine oxidase B (MAO B) has been o bserved in some neurodegenerative diseases, and therefore quantificati on of cerebral MAO B activity by SPECT would be useful for the diagnos is 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 derivativ es of pargyline were synthesized and chemically characterized. The rad ioiodinated ligand [I-125]-2-iodopargyline was obtained with high spec ific activity from the bromo precursor by nucleophilic exchange. Affin ity and selectivity of 2-iodopargyline were tested in vitro. Biodistri bution study of [I-125]-2-iodopargyline was performed in rats. Radioio dinated ligand were obtained in a no-carrier-added form. 2-iodopargyli ne has a higher in vitro affinity for MAO B than pargyline. However, t he 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 bio distribution of [I-125]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thala mus. In conclusion, 2-iodopargyline preferentially binds in vivo to MA O B sites with high affinity. However, its selectivity for MAO B in ra ts is not very high, whereas this ligand binds to a lesser extent to M AO A. It will be then of great value to evaluate the specificity of 2- iodopargyline in humans. This new ligand labeled with I-123 Should the refore be a suitable tool for SPECT exploration of MAO B in the human brain.