6-[F]Fluoro-l--tyrosine

6-[F]Fluoro-l--tyrosine (6-[F]FMT) is a noncatecholic radioligand developed for positron emission tomography (PET) imaging of dopaminergic metabolism and function in the central nervous system (CNS). 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 (1). It is also associated with human behaviors such as reward, reinforcement, and addiction. There are four main dopaminergic pathways in the CNS (2). Two pathways originating in the ventral tegmental area project toward the cortex and the limbic area, a third pathway projects from the hypothalamus projects 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, D-like or D-like (3). The D-like receptor subtypes (D and D) coupled with the Gs protein activate adenylyl cyclase, and the D-like subtypes (D, D, and D) coupled with G proteins inhibit adenylate cyclase. Abnormal changes in the dopaminergic system can lead to pathological conditions such as Parkinson’s disease (PD), schizophrenia, Huntington’s disease, depression, Gilles de la Tourette syndrome, narcolepsy and other neuropsychiatric disorders (4). Radiotracer imaging with specific radiolabeled molecular probes can measure pre-, post-, and intra-synaptic aspects of the dopaminergic system (4). [F]Fluoro-l-dopa ([F]FDOPA) was the first presynaptic probe developed by Firnau et al. (5) and the first molecular probe used by Garnett et al (6). to visualize human brain dopamine . Like endogenous l-DOPA, [F]FDOPA is converted by aromatic l-amino acid decarboxylase (AAAD), an enzyme 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. (7) 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. Three isomers of [F]FMT, 2-, 4-, and 6-[F]FMT, were initially produced and studied (8). 6-[F]FMT appeared most promising as early studies showed that it gave better image contrast and followed the dopaminergic pathway in a manner similar to that of [F]FDOPA (9, 10). However, there is evidence that 6-[F]FMT is distributed in monkey brain regions rich with AAAD-containing monoaminergic neurons which include dopaminergic, serotonergic, and noradrenergic neurons (11).