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6-[18F]fluoro-L-dopa and cerebral blood flow in unilaterally MPTP-treated monkeys
D J Doudet1, R J Wyatt, E Cannon-Spoor
1Clinical Brain Imaging Section, NIMH, Bethesda, MD 20892.
Abstract:
Intravenous administration of 15O-labeled water and 6-[18F]-L-fluorodopa were used to assess abnormal striatal activity in monkeys after long-term recovery of unilateral lesions of the dopaminergic nigro-striatal system induced by the neurotoxin MPTP. PET data were examined in relation to behavioral and biological parameters. Cerebral blood flow and 6-[18F]-L-DOPA uptake were found to be significantly reduced in the lesioned striatum, compared to the unaffected side and to normal controls. There was no correlation between cerebral blood flow and any of the behavioral parameters. The uptake rate constant of 18F-DOPA from blood to striatum and the ratios of striatum to occipital areas were highly correlated to the concentrations of homovanillic acid in the cerebrospinal fluid of the same animals but not to the rotational behavior. This MPTP-induced model of striatal dopamine deficiency in primates presents similarities with idiopathic Parkinson's disease and may be used to evaluate the effects of dopaminergic lesions and transplants on brain function.
Insights
This study used PET scans to assess brain changes in monkeys with MPTP-induced Parkinsonism. Reduced blood flow and dopamine uptake in the striatum correlated with biological markers, not behavior, offering insights into Parkinson's disease models.
Area of Science:
- Neuroscience
- Primate Models
- Dopaminergic System Research
Background:
- Unilateral lesions of the dopaminergic nigro-striatal system were induced using MPTP.
- Long-term recovery and its effects on striatal activity were assessed.
Purpose of the Study:
- To evaluate abnormal striatal activity in MPTP-lesioned monkeys.
- To correlate Positron Emission Tomography (PET) data with behavioral and biological parameters.
Main Methods:
- Intravenous administration of 15O-labeled water and 6-[18F]-L-fluorodopa.
- Positron Emission Tomography (PET) imaging to measure cerebral blood flow and tracer uptake.
- Analysis of cerebrospinal fluid for homovanillic acid concentrations.
Main Results:
- Significantly reduced cerebral blood flow and 6-[18F]-L-DOPA uptake in the lesioned striatum compared to the unaffected side and controls.
- No correlation found between cerebral blood flow and behavioral parameters.
- Uptake rate constant of 18F-DOPA and striatum-to-occipital ratios correlated with homovanillic acid levels, but not rotational behavior.
Conclusions:
- The MPTP-induced primate model mimics aspects of human Parkinson's disease.
- This model is valuable for evaluating interventions for dopaminergic deficits and transplants.
- Striatal dopamine deficiency impacts brain function in ways relevant to Parkinson's disease.