Evaluation of 6-11C-Methyl-m-Tyrosine as a PET Probe for Presynaptic Dopaminergic Activity: A Comparison PET Study with β-11C-l-DOPA and 18F-FDOPA in Parkinson Disease Monkeys.

Abstract

UNLABELLED:

We recently developed a novel PET probe, 6-(11)C-methyl-m-tyrosine ((11)C-6MemTyr), for quantitative imaging of presynaptic dopamine synthesis in the living brain. In the present study, (11)C-6MemTyr was compared with β-(11)C-l-DOPA and 6-(18)F-fluoro-l-dopa ((18)F-FDOPA) in the brains of normal and Parkinson disease (PD) model monkeys (Macaca fascicularis).

METHODS:

PD model monkeys were prepared by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and (11)C-β-CFT was applied to assess neuronal damage as dopamine transporter (DAT) availability. (11)C-6MemTyr, β-(11)C-l-DOPA, or (18)F-FDOPA was injected with and without carbidopa, a specific inhibitor of peripheral aromatic L-amino acid decarboxylase. In normal and PD monkeys, the dopamine synthesis rates calculated using PET probes were analyzed by the correlation plot with DAT availability in the striatum.

RESULTS:

In normal monkeys, whole-brain uptake of β-(11)C-l-DOPA and (18)F-FDOPA were significantly increased by carbidopa at the clinical dose of 5 mg/kg by mouth. In contrast, (11)C-6MemTyr was not affected by carbidopa at this dose, and the metabolic constant value of (11)C-6MemTyr in the striatum was significantly higher than those of the other 2 PET probes. Significant reduction of the presynaptic DAT availability in the striatum was detected in MPTP monkeys, and correlation analyses demonstrated that (11)C-6MemTyr could detect dopaminergic damage in the striatum with much more sensitivity than the other PET probes.

CONCLUSION:

(11)C-6MemTyr is a potential PET probe for quantitative imaging of presynaptic dopamine activity in the living brain with PET.

• Authors: Masakatsu Kanazawa, Hiroyuki Ohba, Norihiro Harada, Takeharu Kakiuchi, Shin-Ichi Muramatsu, Hideo Tsukada
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 57 Issue 2 Pg. 303-8 (Feb 2016) ISSN: 1535-5667 [Electronic] United States
• PMID: 26564319 (Publication Type: Journal Article)
• Copyright: © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• Dopamine Plasma Membrane Transport Proteins
• Enzyme Inhibitors
• O-(11C)methyl-L-tyrosine
• Radiopharmaceuticals
• Receptors, Presynaptic
• fluorodopa F 18
• Tyrosine
• Levodopa
• Dihydroxyphenylalanine
• Carbidopa

Topics

• Animals
• Brain (diagnostic imaging, metabolism)
• Carbidopa (pharmacology)
• Dihydroxyphenylalanine (analogs & derivatives)
• Dopamine Plasma Membrane Transport Proteins (metabolism)
• Dopaminergic Neurons (diagnostic imaging)
• Enzyme Inhibitors (pharmacology)
• Levodopa
• MPTP Poisoning (diagnostic imaging)
• Macaca fascicularis
• Parkinson Disease, Secondary (diagnostic imaging)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals
• Receptors, Presynaptic (metabolism)
• Tyrosine (analogs & derivatives)