This is a competing continuation of grant RO1-NS26621. The investigators have interest in neurotransmitters specifically the aromatic L-amino acid Decarboxylase (AAAD) enzyme, which is involved in the synthesis of dopamine, norepinephrine, and serotonin. The main objective is to develop PET imaging for in vivo assessment of AAAD. They have developed an imaging agent 6-fluoro-m-tyrosine (6FMT), which is taken up into monoaminergic neurons and decarboxylated by AAAD to form metabolites, which do not egress from the brain.
The Specific Aims are: 1) to study 6FMT PET imaging and AAAD activity in rhesus monkey, 2) to study sensitivity and reproducibility issues in humans, and 3) to develop new 6FMT derivative as peripheral AAAD imaging agent. The PET studies will assess the scope and limitation of this technique as a method to evaluate AAAD in the study of neuropsychiatric disorders involving dopamine, nor epinephrine and serotonin. The in vivo imaging technique may assist in understanding etiologies of neuropsychiatric disorders such as Parkinson's disease, schizophrenia, substance abuse, anxiety and bipolar disorders.
| Murali, D; Flores, L G; Roberts, A D et al. (2003) Aromatic L-amino acid decarboxylase (AAAD) inhibitors as carcinoid tumor-imaging agents: synthesis of 18F-labeled alpha-fluoromethyl-6-fluoro-m-tyrosine (FM-6-FmT). Appl Radiat Isot 59:237-43 |
| Stein, T D; DeJesus, O T (2000) Effect of 6-fluoro-m-tyrosine on dopamine release and metabolism in rat striatum using in vivo microdialysis. Brain Res 884:192-5 |
| Brown, W D; DeJesus, O T; Pyzalski, R W et al. (1999) Localization of trapping of 6-[(18)F]fluoro-L-m-tyrosine, an aromatic L-amino acid decarboxylase tracer for PET. Synapse 34:111-23 |
| Endres, C J; Swaminathan, S; DeJesus, O T et al. (1997) Affinities of dopamine analogs for monoamine granular and plasma membrane transporters: implications for PET dopamine studies. Life Sci 60:2399-406 |
