[F-18]fluoro-beta-fluoromethylene-m-tyrosine derivatives show stereo, geometrical, and regio specificities as in vivo central dopaminergic probes in monkeys

Stereo (D and L), geometrical (E and Z), and regiospecific (2-, 4-, and 6-[ F-18]fluoro) analogs of beta-fluoromethylene-m-tyrosine (FMMT) have been in vestigated in adult vervet monkeys (Cercopithecus aethiops sabaeus, n = 12) in vivo with positron emission tomography (PET). Brain transport through t he blood-brain barrier and central aromatic amino acid decarboxylase (AAAD) -mediated decarboxylation rates were established. Results show strict struc tural dependency of the kinetic behavior of radiofluorinated FMMT analogs, with the E-isomer exhibiting a higher specificity over the (Z) geometrical counterpart for central dopaminergic structures. The 6-[F-18]fluoro substit uted L-(E)-FMMT was also favored over the 2- and 4-[F-18]fluorosubstituted isomers in terms of their ability to localize in the same brain areas. The role of PET in drug development is also exemplified in this work. NUCL MED BIOL 26;4:365-370, 1999. (C) 1999 Elsevier Science Inc. All rights reserved .