Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, and the Laboratory of Structural Biology and Molecular Medicine, Los Angeles, California, U.S.A.

Correspondence: Jorge R Barrio, UCLA School of Medicine, Department of Molecular and Medical Pharmacology, Division of Nuclear Medicine, B2-086A CHS, Los Angeles, CA 90095, U.S.A.

Received 31 May 1995; Revised 19 October 1996; Accepted 20 October 1995.

Abstract

In this work, we introduce 6-[¹⁸-fluoro-L-m-tyrosine(6-FMT) and compare its in-vivo kinetic and biochemical behaviors in monkeys and rodents with those of 4-FMT and 6-[¹⁸F]fluoro-L-3,4-dihydroxyphenylalanine (DOPA) (FDOPA). These radiofluorinated m-tyrosine presynaptic dopaminergic probes, resistant to peripheral 3-O-methylation, offer a nonpharmacological alternative to the use of catechol-O-methyltransferase inhibitors. Like FDOPA, 4-FMT and 6-FMT are analogs that essentially follow the L-DOPA pathway of central metabolism. After i.v. administration in nonhuman primates and rodents, these new radiofluorinated m-tyrosine analogs accumulate selectively in striatal structures and allow for the detection of additional innervation sites (e.g., brain stem) rich in aromatic amino acid decarboxylase. Biochemical analyses in rodents and monkeys revealed the specificity of their central and peripheral metabolism. Molecular and enzymatic mechanisms involved in their retention in central brain structures are consistent with involvement of dopaminergic neurons. The high signal-to-noise ratios observed make these radiofluorinated m-tyrosine analogs outstanding candidates for probing the integrity of central dopaminergic mechanisms in humans.