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Evaluation of Fluorinated m-Tyrosine Analogs as PET Imaging Agents of Dopamine Nerve Terminals: Comparison with 6-Fluorodopa

Department of Medical Physics and Department of Psychiatry, University of Wisconsin Medical School, Madison, Wisconsin

Correspondence: For correspondence or reprints contact: Onofre T. DeJesus, MD, Dept. of Medical Physics, University of Wisconsin Medical School, 1530 Medical Sciences Center, 1300 University Ave., Madison, Wl 53706.

ABSTRACT

Fluorinated m-tyrosine analogs were evaluated as PET imaging agents and compared with 6-fluoroDOPA in the visualization of dopamine nerve terminals. Methods: 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). Results: 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. Conclusion: 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.

Key Words: fluoro-m-tyrosine • 6-fluoro-L-DOPA • positron emission tomography • dopamine neurons

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