Abstract
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Objectives: The goal of this study was to monitor the effectiveness of stem cell therapy in Parkinson’s disease (PD) using PET imaging of substantia nigra with F-18-dihydrotetrabenazine (F-18-DTBZ), which has a high binding affinity (nm) for vesicular monoamine transporter 2.
Methods: PD was induced in normal adult, male rats by unilateral intracerebral injection of the dopamine neurotoxin 6-hydroxydopamine (Sigma; 20μg in 4μl PBS) into right median forebrain bundle. Motor function was evaluated at 3 and 6 weeks intervals following amphetamine (5mg/kg, i.p.) challenge and F-18-DTBZ PET imaging was performed (MOSAIC, Phillips). Rats with a motor deficit (rotational score ≥ 50/5 min, automated rotometer system) and lacking F-18-DTBZ uptake in the striatum ipsilateral to the lesion were surgically implanted either with 1x106 differentiated human embryonic stem cells (Wicell H9 line) or with 5x105 14d mouse fetal substantia nigra cells. Rats were monitored for motor function and periodical F-18-DTBZ PET imaging was performed. Normal striatum to treated striatum and striatum to cerebellum F-18 uptake ratios were calculated.
Results: The F-18-DTBZ uptake in normal striatum was 2.6 ± 0.2 times greater than cerebellum. In PD rats (≥ 50 rotations/5 min), this uptake was only 1.05 ± 0.05. The F-18 uptake in normal striatum was >2 in that of the lesioned striatum. The longitudinal studies to determine the effectiveness of stem cell therapy as determined by measurements of striatum uptake vs rotational score are in progress.
Conclusions: PET imaging with F-18-DTBZ provides a promising tool to monitor the effectiveness of stem cell therapy in PD.
- Society of Nuclear Medicine, Inc.