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Positron emission tomography with 4-[18F]fluoro-L-m-tyrosine in MPTP-induced hemiparkinsonian monkeys
N Hayase1, K Tomiyoshi, K Watanabe
1Department of Neurosurgery and Nuclear Medicine, Gunma University School of Medicine, Japan.
Abstract:
PET imaging studies with 4-[18F]fluoro-L-m-tyrosine (FMT) in normal macaca monkeys showed selective accumulations of radioactivity in the striatum with time. In monkeys rendered hemiparkinsonian by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), FMT uptake was eliminated in the lesioned striatum. FMT-PET studies were able to detect dopaminergic terminals in both normal and hemiparkinsonian monkeys, and clearly showed a reduction in aromatic L-amino acid decarboxylase (AAAD) activities in the MPTP-lesioned striatum. These results show that FMT is promising as a PET tracer for the evaluation of central dopaminergic systems in parkinsonism.
Insights
4-[18F]fluoro-L-m-tyrosine (FMT) positron emission tomography (PET) effectively detects dopaminergic terminals. FMT uptake reduction in hemiparkinsonian monkeys indicates its potential for evaluating parkinsonism.
Area of Science:
- Neuroscience
- Radiochemistry
- Medical Imaging
Background:
- Parkinsonism is a neurodegenerative disorder affecting dopaminergic systems.
- Accurate assessment of dopaminergic terminal integrity is crucial for diagnosis and treatment monitoring.
- Positron Emission Tomography (PET) offers a non-invasive method for in vivo imaging of neurochemical processes.
Purpose of the Study:
- To evaluate 4-[18F]fluoro-L-m-tyrosine (FMT) as a PET tracer for assessing central dopaminergic systems.
- To investigate FMT uptake in normal and hemiparkinsonian primate models.
- To determine the correlation between FMT uptake and aromatic L-amino acid decarboxylase (AAAD) activity.
Main Methods:
- PET imaging was performed in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian macaca monkeys.
- Radioactivity accumulation of FMT was measured over time in the striatum.
- AAAD activity was assessed in relation to FMT uptake in lesioned and normal striata.
Main Results:
- Selective accumulation of FMT radioactivity was observed in the striatum of normal monkeys.
- FMT uptake was significantly reduced in the MPTP-lesioned striatum of hemiparkinsonian monkeys.
- FMT-PET studies demonstrated reduced AAAD activities in the MPTP-lesioned striatum, correlating with dopaminergic terminal loss.
Conclusions:
- FMT is a promising PET tracer for visualizing and quantifying central dopaminergic terminals.
- FMT-PET imaging can effectively detect alterations in dopaminergic systems characteristic of parkinsonism.
- This tracer holds potential for evaluating the efficacy of therapies targeting parkinsonism.