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A non-human primate model for stable chronic Parkinson’s disease induced by MPTP administration based on individual behavioral quantification


Jincheol Seo et al., Journal of Neuroscience Methods, 2019


Parkinson’s disease (PD) is a neurodegenerative disease that affects about 3% of the population over 65 years of age. PD is characterized by a selective loss of dopaminergic neurons accompanied by movement disorders, including rigidity, bradykinesia, akinesia, tremors, and postural instability.

The authors aimed to develop a MPTP-induced chronic NHP model with stable symptoms by adjusting MPTP treatment based on individual behavioral quantification using a video-based analysis system. To validate this strategy, they assessed a parkinsonian behavior score, an immunohistochemistry Western blot, and PET imaging of dopamine transporter (DAT) with [18F] N-(3-fluoropropyl)-2ß-carboxymethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT).

The authors stated that the novel strategy of MPTP administration based on global activity evaluations using a video-based analysis system provides an important conceptual advance of this method for the development of chronic NHP PD models.

Results from nanoScan® PET/CT

Mediso’s nanoScan PET/CT with 16cm bore size, 12 cm transaxial and 10 cm axial Field of View (FOV) were suitable to execute PET/CT scans in cynomolgus monkeys (Macaca fascicularis). Furthermore high spatial and temporal resolution of PET allowed to determine the dopamine transporter biding potential (BP) in different striatal sub-regions.

Following a CT scan for attenuation correction, 185 MBq 18 F-FP-CIT in 1.5 ml saline was injected intravenously via the saphenous vein. To monitor presynaptic dopamine transporter activity in vivo, serial 18F-FP-CIT PET imaging was performed after MPTP administration.

  • The biding potential analysis revealed that the 18F-FP-CIT BP were significantly reduced in all sub-regions of the striatum at 8, 16, 24, 32,40 and 48 weeks following the first MPTP administration (Fig. 4A and 4B).
  • Monkeys with fewer striatal DAT tended to have lower global activity (GA), indicating that a decrease in GA reflects damage in dopaminergic neurons.
  • The severity of Parkinsonian symptoms and the loss rates of DAT in each striatal sub-region did not correlate with the total dose of MPTP, indicating that a fixed MPTP dose is not a good strategy for development of chronic NHP PD models

Fig. 4. (A) Representative 18F-FP-CIT PET images fused with individual MRI. (B) Histogram representing 18F-FP-CIT binding potential (BP) in the MPTP-injection group. (#P < 0.05, *P<0.01 vs. baseline). (C) Histogram representing time activity curve. The radiotracer uptake in each region of interest was estimated as the standardized uptake value (SUV), which was calculated as decay-corrected activity per milliliter of tissue volume per injected radiotracer activity per body mass ([kBq/mL]/[kBq/g]). Ant, anterior; binding potential, BP; Ext, external; pallidum, globus pallidus; Int, internal; Post, posterior.

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