Possible correlation between imaging biomarker, Parkinson’s severity

18F-DTBZ PET is a potential imaging biomarker for measuring dopaminergic degeneration in vivo and monitoring Parkinson disease (PD) severity, according to a study published by JAMA Neurology on June 9.

Diagnosing PD is typically based on clinical criteria characterized by motor symptoms like bradykinesia, rigidity, resting tremor and postural instability. “A noninvasive neuroimaging technique with radiotracers targeting the dopaminergic system from both PET and single-photon emission CT is an ideal method to monitor disease severity and investigate neural degeneration in PD,” wrote the study’s lead author, Ing-Tsung Hsiao, PhD, of Chang Gung University in Taoyan, Taiwan, and colleagues.

Vesicular monoamine transporter type 2 (VMAT2) distribution’s image features were investigated during the study by using 18F-DTBZ PET ([18F]9-fluoropropyl-(+)-dihydrotetrabenazine) in patients with different stages of PD and comparing with a healthy control cohort. The researchers investigated 2D and 3D distribution patterns of VMAT2 in patients with mild, moderate and advanced stages of the disease to reveal the spatial and progressive change of dopaminergic degeneration. They also analyzed correlations between clinical motor disability and the reduction of VMAT2 availability.

The study recruited 17 healthy control participants and 53 patients divided into groups of mild, moderate and advanced stages of PD for 18F-DTBZ PET scans. To quantify disease severity in the patients with PD, the researchers used the modified Hoehn-Yahr Scale, Unified Parkinson Disease Rating Scale total scores and subscores of posture instability and gait disturbance, tremor, akinesia and rigidity while not taking medication.

Once voxelwise and volume of interest-based image analyses were performed and specific uptake ratio (SUR) of each volume of interest and voxel were calculated, results from the 18F-DTBZ PET images showed an obvious correlation between the reduction of vesicular monoamine transporter type 2 availability and disease severity.

For the mild PD group, the mean reductions of vesicular monoamine transporter type 2 density for the caudate, putamen and substantia nigra were 21.5 percent, 58.2 percent and 21.1 percent, respectively. In the moderate group, these numbers were represented as 60.75 percent, 79.49 percent and 39.87 percent. Lastly, the density for the advanced PD group for the caudate, putamen and substantia nigra group were 63.94 percent, 83.2 percent and 44 percent.

The SURs of bilateral striatal regions showcased significantly exponential correlations to stage, disease duration, Unified Parkinson Disease Rating Scale motor score, posture instability and gait disturbance, and akinesia, rigidity and tremor scores.

“In PD, the severe reduction of VMAT2 density in the nigrostriatal system makes the effect of occipital hypoperfusion on the quantification of striatal regions too minimal to be neglected,” wrote Hsiao and colleagues. “Therefore, we suggest that the quantification of VMAT2 availability in extrastriatal regions should be more cautious when using the occipital lobe as a reference region in disease with occipital hypoperfusion or atrophy.”

The authors propose the need for future work assessing correlation of cognitive and mood performances to the VMAT2 distributions using 18F-DTBZ PET imaging.