4-[F]Fluoro-l--tyrosine

4-[F]Fluoro-l--tyrosine (4-[F]FMT) is a noncatecholic radioligand developed for positron emission tomography (PET) imaging of dopaminergic metabolism and function in the central nervous system (CNS) (1, 2). It is an analog of dihydroxyphenylalanine (l-DOPA) labeled with F, a positron emitter with a physical of 109.7 min. Dopamine is an important neurotransmitter that regulates and controls human movement, motivation, and cognition (3). It is also associated with human behaviors such as reward, reinforcement, and addiction. There are four main dopaminergic pathways in the CNS (4). Two pathways that originate in the ventral tegmental area project toward the cortex and the limbic area, a third pathway projects from the hypothalamus toward the pituitary gland, and a fourth pathway projects from the substantia nigra to the striatum. Neurons located in these pathways release dopamine as a neurotransmitter at their terminals. There are five known dopamine receptor subtypes, which are categorized as D-like or D-like (5). The D-like receptor subtypes (D and D) couple with the Gs protein to activate adenylyl cyclase, and the D-like subtypes (D, D, and D) couple with G proteins to inhibit adenylate cyclase. Abnormal changes in the dopaminergic system can lead to pathologic conditions such as Parkinson’s disease, schizophrenia, Huntington’s disease, depression, Gilles de la Tourette syndrome, narcolepsy and other neuropsychiatric disorders (6). Radiotracer imaging with specific radiolabeled molecular probes can measure pre-, post-, and intrasynaptic aspects of the dopaminergic system (6). [F]Fluoro-l-dopa ([F]FDOPA), which was developed by Firnau et al. (7), was the first presynaptic probe to be developed. It was also the first molecular probe used by Garnett et al. (8) to visualize human brain dopamine . Like endogenous l-DOPA, [F]FDOPA is converted by the enzyme aromatic l-amino acid decarboxylase (AAAD) to the dopamine analog fluorodopamine. Thus, PET imaging of [F]FDOPA allows visualization and assessment of dopamine function in the brain. However, the use of [F]FDOPA is complicated by the peripheral metabolism of this agent. DeJesus et al. (9) proposed the synthesis and use of [F]FMT and other tyrosine analogs as possible alternative dopamine probes because they lack the enediol moiety required of catecholamine--methyltransferase (COMT) substrates. Both - and -tyrosines are excellent substrates for AAAD but -tyrosine is a normal constituent in the brain (10). Three isomers of [F]FMT, 2-, 4-, and 6-[F]FMT, were initially produced and studied (11) Both 4-[F]FMT and 6-[F]FMT appeared promising as early studies showed that they provided good image contrast (1, 12, 13).