Evaluation of 3-[¹⁸F]Fluoro-α-fluoromethyl-p-tyrosine as a tracer for striatal tyrosine hydroxylase activity

3-[¹⁸F]Fluoro-α-fluoromethyl-p-tyrosine (3-F-FMPT) was evaluated as a tracer for CNS tyrosine hydroxylase (TH) activity in rodents and in a rhesus monkey. Results of in vitro experiments using rat striatal homogenates showed that the introduction of fluorine into the 3-phenyl position did not significantly alter the ability of FMPT to act as a TH-activated l-aromatic amino acid decarboxylase (l-AAAD) inhibitor. These studies further showed that 3-F-FMPT-induced l-AAAD inhibition was dose-dependent. Furthermore, striatal homogenates prepared from rats pretreated with the potent TH inhibitor α-methyl-p-tyrosine was found to have diminished 3-F-FMPT-induced l-AAAD inhibition. However, despite these promising in vitro results, the biodistribution of this compound in mice showed low brain uptake and fast clearance through the kidneys. A PET study using a Rhesus monkey injected with 3-[¹⁸F]F-FMPT confirmed the results obtained in mice, i.e. negligible brain uptake but high localization in the bladder. We conclude that 3-[¹⁸F]F-FMPT would not be useful as a tracer for cerebral TH activity.