Objective: To investigate the mapping of metabotropic glutamate receptor subtype 1 (mGluR1) in elderly normal and de novo patients with Parkinson’s disease (PD) using N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-¹¹C methoxy-N-methylbenzamide (¹¹C-ITMM) and positron emission tomography (PET), and to assess whether mGluR1 is involved in the damaged dopaminergic system in PD.

Background: Glutamate receptors are divided into 2 types based on their biological functions and molecular structures; ionotropic and metabotropic types. The metabotropic type is classified into 3 groups, including 8 subtypes. The mGluR1 is one of the group 1 receptors, localized postsynaptically in the cerebellar Purkinje cells, striatonigral and striatopallidal projection neurons, and striatal interneurons. However, the relationship between the mGluR1 and PD remains to be determined.

Methods: We studied 25 normal subjects (13 men and 12 women, mean age ± SD, 69.2 ± 7.1 y.o.) and 10 de novo patients with PD (6 men and 4 women, 70.5 ± 7.3 y.o.). Informed consent was obtained from all subjects. PET was performed with a Discovery PET/CT 710 (GE Healthcare). A dynamic series of decay-corrected PET scans was performed for 90 minutes starting at the time of the injection of 700 MBq of ¹¹C-ITMM. We generated early images for ¹¹C-ITMM by summing frames of the dynamic scan from 0 to 10 minutes. The MRI image was 3-dimensionally registered to the early image of each subject. The early images and the registered MRI images were used as references for placing regions of interest (ROIs) on PET images from dynamic scans. Circular ROI of 10-mm in diameter were placed on the PET images. We calculated regional time activity curves in the tissue (tTACs) from the dynamic data and ROIs, and we evaluated binding of ¹¹C-ITMM to mGluR1s in the regions as a distribution volume ratio (DVR) using tTACs, a graphical analysis with the occipital lobe as the reference region (1). The level of significance was set at p<0.05.

Results: The DVR of the patients was significantly lower than the controls in the cerebellar hemisphere, and temporal and parietal lobe.

Conclusions: The results may be involved in motor symptoms or compensation for the decrease in dopamine. To clarify this issue, further PET studies will be needed, such as involvements in severity and asymmetry of parkinsonism.

1. Toyohara J, et al., Nucl Med Biol 40, 214-220, 2013.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/density-of-metabotropic-glutamate-receptors-subtype-1-in-de-novo-patients-with-parkinsons-disease-using-11c-itmm-pet/