Evaluation of fluorinated m-tyrosine analogs as PET imaging agents of dopamine nerve terminals: comparison with 6-fluoroDOPA.

Abstract

Fluorinated m-tyrosine analogs were evaluated as PET imaging agents and compared with 6-fluoroDOPA in the visualization of dopamine nerve terminals. The three m-tyrosine analogs, 6-[18F]fluoro-L-m-tyrosine (6-FMT), 2-[18F]fluoro-L-m-tyrosine (2-FMT) and 6-[18F]fluoro-fluoromethylene-DL-m-tyrosine (6-F-FMMT), were prepared via electrophilic radiofluorination using [18F]acetylhypofluorite. These three analogs, as well as 6-[18F]fluoro-L-DOPA (6-FD), were injected into sets of rhesus monkeys, and serial PET images were acquired. Plasma samples were collected at different times after tracer administration, and metabolite analyses were done using high-performance liquid chromatography (HPLC). Visual inspection of the PET images obtained using these four tracers showed that the best image contrast was obtained with 6-FMT. Patlak analysis with a reference tissue input function yielded a mean uptake rate constant for 6-FMT of 0.019 min-1, a value twice those for the other tracers including 6-FD. These results demonstrate the superiority of 6-[18F]FMT in visualizing dopamine terminals in the rhesus monkey brain and suggest that 6-[18F]FMT is the tracer of choice in the assessment of dopamine metabolism in the living human brain.