Positron emission tomography (PET) is an imaging tool that is widely used to diagnose several conditions such as cancer, heart disease, and brain disease.
The technique has many uses in Parkinson’s disease including early and accurate diagnosis, determining disease severity by identifying anatomical changes in different brain regions, identifying mechanisms that may be responsible for the motor and non-motor symptoms of the disease, and evaluating patient response to medication.
PET is a relatively expensive technique but offers higher sensitivity and higher spatial and temporal resolution than other imaging techniques. Recently, a new brain scanner, which is about 10 times less expensive and much smaller than other models, has been developed that can overcome the limitations of the currently available models.
How a PET scan is performed
A PET scan involves the injection of a radioactive compound called a tracer into the bloodstream of the patient, which travels to the brain and other parts of the body. Then a 3D image of the brain that shows the distribution of the tracer in different areas is generated. A trained physician can interpret the images and determine the pathology involved.
There are several PET tracers available that can be used to functionally dissect different aspects of Parkinson’s disease such as disease status, progression, response to therapy, and metabolic changes in different parts of the brain.
For example, a PET scan can be performed using an imaging compound called 18F-DOPA on a suspected Parkinson’s patient who has motor symptoms such as tremor and gait disturbance.
18F-DOPA is a precursor of dopamine, a neurotransmitter or cell signaling molecule that is significantly reduced in Parkinson’s disease due to the death of dopamine-producing nerve cells in a region of the brain called the substantia nigra. 18F-DOPA can cross the blood-brain barrier and be converted to dopamine.
Once 18F-DOPA is fully absorbed, a scan is performed. For the scan, the patient lies flat on a table, which slides into a large tunnel-shaped scanner. A computer then generates 3D images of the brain that can be visualized on a monitor. These images show the uptake and distribution of 18F-DOPA in different parts of the brain. The patterns indicate physiological activity. In early Parkinson’s disease, PET images will show a reduced uptake of 18F-DOPA in the substantia nigra region of the brain.
PET scans and Parkinson’s pathology
The pathophysiological mechanism underlying Parkinson’s disease is complex. However, a wide variety of radiotracers are available that can provide insight into the different characteristics of disease pathology.
18F-DOPA uptake reflects the ability of dopamine-producing neurons to produce dopamine in the brain. Studies have shown that 18F-DOPA uptake correlates with increased bradykinesia and rigidity but not with tremor.
Motor dysfunction can be assessed by using PET tracers such as 18F-DOPA and radiolabeled tracers specific for dopamine transporters (DaT) and vesicular monoamine transporters (VMAT). Both DaT and VMAT are membrane-embedded proteins involved in the uptake of monoamine neurotransmitters such as dopamine at the synapse, the point of contact between two nerve cells or a nerve cell and a muscle cell. Abnormal activity of these transporters can be seen by PET and used for early diagnosis of Parkinson’s.
PET is also valuable for differentiating Parkinson’s disease from other movement disorders. For example, 18F-DOPA PET has been used to differentiate between drug-induced and idiopathic Parkinson’s disease. Drug-induced Parkinsonism is a reversible condition, which can occur when antipsychotics are taken. Presynaptic DaT activity is not affected in the brains of the drug-induced Parkinson’s patient, whereas idiopathic Parkinson’s patients show decreased DaT activity even in the early stages of the disease.
PET using another tracer called 18F-FDG can be used to differentiate between patients with Parkinson’s disease and those with multiple striatal atrophy (MSA) because the uptake of 18F-FDG in the brains of MSA patients is low, whereas its uptake in Parkinson’s patients is either normal or increased.
About 40 percent of Parkinson’s disease patients have dementia, which is associated with changes in the cortical region of the brain. PET studies with18F-FDG can, even in the early stages of Parkinson’s disease, differentiate between patients who have dementia — because they have low activity in the cortical region — and those who do not have dementia. Studies also showed reduced glucose metabolism as evaluated by the uptake of 18F-FDG in the frontal, temporal, and parietal areas of the brain in Parkinson’s disease patients with dementia compared with those who don’t have dementia.
Ongoing clinical trials
There are several clinical trials underway using PET scans to further discover mechanisms underlying the pathology of Parkinson’s disease and its potential cure.
The National Institute of Mental Health is conducting PET studies (NCT00024622) with 18F-DOPA and H215O radiotracers in a single-scan session to distinguish patients with familial and sporadic Parkinson’s disease. This study began in September 2001 and is still recruiting participants in Maryland.
Avid Radiopharmaceuticals, in collaboration with the University of Pennsylvania, is conducting a prospective study (NCT03143374) that uses PET scans to measure the amount of tau protein in the brains of patients with Alzheimer’s disease, Parkinson’s disease, Lewy body disease, and frontotemporal dementia. Aggregates of tau protein in the brain, especially in areas that control memory, is a characteristic feature of dementia in Alzheimer’s disease patients. The buildup of tau protein aggregates in the brain can also be used to diagnose patients developing dementia in Parkinson’s and other diseases. This study started in September 2016 and is still recruiting participants in Pennsylvania.
The Washington University School of Medicine, in collaboration with the National Institutes of Health, is conducting a prospective case-control study (NCT02763683) using a brain imaging method called Pittsburgh B PET and vesicular cholinergic transport PET to identify individuals with Parkinson’s disease who are at risk of developing dementia and identify the underlying cause of dementia. This study started in June 2016 and is still recruiting participants in Missouri.
Because exercise is often reported to be therapeutic for Parkinson’s patients, the Pacific Parkinson’s Research Centre is conducting a randomized clinical trial (NCT02265900) using PET scanning to identify potential mechanisms by which exercise may be beneficial for the treatment of the disease. The study began in November 2014 and is still recruiting in Canada.
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