Novel agent emerges for early Parkinson’s

A new imaging agent is showing potential for the early detection of Parkinson’s disease (PD) by identifying a functional loss of dopamine neurons, according to a study published online Nov. 28 by the Journal of Nuclear Medicine.

PD is the second-most prevalent neurodegenerative disorder and affects 1-3 percent of the population over the age of 80. Misdiagnosis of the disease may be occurring in up to 30 percent of early cases of disease, making a stronger case for molecular neuroimaging of PD. Shao-Cheng Lin, a scientist from the department of neurology at Chang Gung Memorial Hospital, Taoyuan, Taiwan, and colleagues tested the feasibility of imaging a mechanism of monoaminergic degeneration thought to be involved in Parkinson’s pathology with PET and the agent F-18 9-Fluoropropyl-(1)-Dihydrotetrabenzazine (F-18 DTBZ). The radioligand hones in on vesicular monoamine transporter type 2 (VMAT2), a membrane protein charged with transporting monoamines, especially neurotransmitters including dopamine, serotonin and norepinephrine, from within the cell into the synaptic vesicle. The density of VMAT2 is directly related to the health of dopamine neurons located in the substantia nigra of the brain stem. Typical PD pathology is represented by a substantial decline in dopaminergic neurons in this area. Imaging lagging VMAT2 density with this agent may provide a clearer picture of the beginning stages of Parkinson’s.

“Our study suggested that F-18 DTBZ PET was an excellent tool in differentiating PD from normal aging in the early stage of disease,” wrote Lin et al. “The notable decline of F-18 DTBZ uptake in the ipsilateral striatum suggested that F-18 DTBZ PET might serve as an in vivo biomarker to detect the monoaminergic degeneration in the pre-motor phase of PD.”

For this study, a total of 30 patients with PD and 17 matched healthy controls were imaged with PET and F-18 DTBZ. Results showed that specific uptake ratios were significantly lower in the bilateral caudate, anterior putamen, posterior putamen, substantia nigra and nucleus accumbens of PD subjects. Ratios were particularly lower, 81 percent, in the posterior putamen on the opposite side of the symptomatic region of the brain. Uptake ratios in the contralateral anterior putamen and bilateral posterior putamen showed 100 percent sensitivity and specificity for distinguishing PD patients from healthy controls.

There were two noted limitations of the agent. Firstly, F-18 DTBZ is produced via cyclotron at a relatively high cost. Secondly, VMAT2 availability may be influenced by dopamine treatments in advanced cases. Further studies are required to validate these findings before there could be any change in the clinical diagnosis of Parkinson’s.