PET Imaging for Parkinson's Disease

Overseen By Evan Hudson

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: High radiation exposure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a new compound, \[18F\]DPA-714, behaves in the brains of individuals with early signs of Parkinson's Disease (PD) and those with a confirmed diagnosis, compared to healthy individuals. Researchers seek to observe changes in this compound over a two-year period in participants who have not started PD treatment. The goal is to better understand PD progression and how it might be detected or monitored. Participants should be part of a specific PD study, not yet on PD medication, and able to undergo a PET scan.

As an Early Phase 1 trial, this research focuses on understanding how the new compound works in people, offering participants a unique opportunity to contribute to groundbreaking PD research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants should not have started symptomatic treatment for Parkinson's Disease at the time of enrollment or during the first 2 years of participation.

What prior data suggests that this protocol is safe for participants?

Research has shown that [18F]DPA-714 has been tested for safety in both animals and people with Parkinson's disease. These studies found the tracer safe for imaging and without harmful effects, indicating that [18F]DPA-714 is generally well-tolerated in humans. The tracer aids researchers in studying brain inflammation related to Parkinson's by tracking specific proteins in the brain. Although this trial is in its early stages, the positive results from previous studies encourage its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for Parkinson's disease focus on managing symptoms through medications like levodopa, which helps replenish dopamine. However, [F-18]DPA714 is different because it uses a radiolabeled compound for PET imaging to potentially identify inflammation in the brain, which might play a role in the progression of Parkinson's. Researchers are excited because this could lead to earlier and more precise diagnosis, helping to tailor treatments better for individuals and possibly slowing down the disease's progression.

What evidence suggests that this protocol is effective for Parkinson's Disease?

This trial will use [18F]DPA-714, a PET imaging marker, to assess its effectiveness in detecting microglial activation, a key feature of Parkinson's Disease. Studies have shown that [18F]DPA-714 is more selective and reliable than other imaging methods for identifying brain changes linked to the disease. It binds to a protein called TSPO, which appears in higher amounts in inflamed areas, common in Parkinson's. Research indicates that this tracer can help track disease progression by revealing these changes over time. Initial human studies also suggested it is stable and safe for use in the body. ^{1 2 6 7 8}

Who Is on the Research Team?

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

David Standaert, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage or prodromal Parkinson's Disease, as well as healthy volunteers. Participants will be monitored over a 24-month period to track changes in their condition.

Inclusion Criteria

Able to provide informed consent

I have Parkinson's and haven't started treatment for symptoms yet or within the first 2 years of joining the study.

Highly effective method of birth control is defined as practicing at least one of the following: A birth control method that results in a less than 1% per year failure rate when used consistently and correctly, such as oral contraceptives for at least 3 months prior to injection, an intrauterine device (IUD) for at least 2 months prior to injection, or barrier methods, e.g., diaphragm or combination condom and spermicide. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable

Exclusion Criteria

Any other medical or psychiatric condition or lab abnormality, which in the opinion of the Site Investigator might preclude participation

Exposure to a total effective dose equivalent of 50 millisievert (mSv) for the whole body, which is the annual limit established by the US Code of Federal Regulations, during the past year

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline TSPO-PET imaging to measure regional brain TSPO levels

1 visit

1 visit (in-person)

Longitudinal Imaging

Participants undergo TSPO-PET imaging to assess changes in neuroinflammation at 12 and 24 months

24 months

2 visits (in-person) at 12 and 24 months

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [F-18]DPA714

Trial Overview [18F]DPA-714, an imaging compound, is being tested through IV administration to see how it binds in the brain of those with Parkinson's compared to healthy people and how this binding changes over two years.

How Is the Trial Designed?

Group I: Prodromal and manifest (PD) participants Experimental Treatment 1 Intervention

Group II: Healthy participants Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Michael J. Fox Foundation for Parkinson's Research

Collaborator

Trials

117

Recruited

537,000+

Published Research Related to This Trial

In a study involving 24 Parkinson's disease (PD) patients and 28 healthy controls, the use of the radioligand [18F]-DPA714 revealed significantly higher microglial activation in specific brain regions of PD patients, indicating a neuroinflammatory response associated with the disease.

Despite the observed microglial activation, there was no correlation between the level of activation and the severity of motor symptoms or disease duration, suggesting that while neuroinflammation is present, it may not directly influence clinical outcomes in PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging. Lavisse, S., Goutal, S., Wimberley, C., et al.[2021]

The study developed a molecular imaging probe, [18F]DPA714, which effectively targets the 18-kDa translocator protein (TSPO) to monitor microglia activation and neuroinflammation in an Alzheimer's disease mouse model, showing a significant increase in uptake in affected brain regions compared to control mice.

Quantitative PET imaging revealed that [18F]DPA714 uptake was significantly higher in the cortex and hippocampus of APP/PS1 mice at 12-13 and 15-16 months of age, indicating its potential utility in determining optimal timing for anti-inflammatory therapies in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging for Dynamically Monitoring Neuroinflammation in APP/PS1 Mouse Model Using [18F]DPA714. Hu, W., Pan, D., Wang, Y., et al.[2020]

Both 18 F-FP-CIT PET and 123 I-FP-CIT SPECT imaging effectively show reduced dopamine transporter uptake in patients with Parkinson's disease (PD), indicating their potential as biomarkers for early diagnosis.

The meta-analysis included 779 PD patients and 124 healthy controls for PET studies, and 1244 PD patients and 859 controls for SPECT studies, demonstrating significant reductions in dopamine transporter uptake in key brain regions associated with PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging of dopamine transporters in Parkinson disease: a meta-analysis of 18 F/123 I-FP-CIT studies. Kong, Y., Zhang, C., Liu, K., et al.[2021]

Using high-resolution PET/CT scans with 18F-FDOPA and 11C-raclopride, this study found that both tracers showed higher uptake in normal subjects compared to previous studies, indicating improved imaging capabilities.

The study demonstrated that 18F-FDOPA uptake in the substantia nigra can be clearly visualized, providing valuable insights for evaluating regenerative therapies in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A revisit to quantitative PET with 18F-FDOPA of high specific activity using a high-resolution condition in view of application to regenerative therapy. Akamatsu, G., Ohnishi, A., Aita, K., et al.[2017]

Current molecular PET imaging techniques for neurodegenerative parkinsonism focus on radiotracers that visualize vulnerable neuron terminals, but they do not effectively differentiate between various parkinsonian conditions based on neurotransmitter loss.

Research is ongoing to develop new imaging ligands using advanced molecular modeling to better target specific proteinopathies associated with these disorders, although current PET imaging methods face challenges such as the need for automated analysis and limited insurance coverage in the U.S.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Imaging of Neurodegenerative Parkinsonism. Frey, KA., Bohnen, NILJ.[2021]

In a study involving 24 patients with idiopathic Parkinson's disease and 18 healthy controls, dual time point F-18 FP-CIT PET imaging effectively diagnosed Parkinson's disease by showing significantly reduced striatooccipital ratios in the patients.

The results indicated that the 90-minute PET scan alone is sufficient for diagnosing Parkinson's disease, as it provided comparable diagnostic value to the 210-minute scan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Significance of F-18 FP-CIT Dual Time Point PET Imaging in Idiopathic Parkinson's Disease. Oh, JK., Yoo, ID., Seo, YY., et al.[2021]

18F-Dopa PET is a highly sensitive imaging technique that helps diagnose Parkinson's disease by quantifying the loss of dopaminergic fibers, allowing for objective tracking of disease progression.

PET studies reveal that the akinesia (difficulty in movement) associated with Parkinson's is linked to reduced activation in key brain areas responsible for motor preparation, which can be restored through treatments like dopaminergic medication or surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor disturbance and brain functional imaging in Parkinson's disease. Brooks, DJ.[2018]

The study found that the PET radiotracer [18F]AV-1451 binds to neuromelanin in the substantia nigra, showing a significant decrease in binding in patients with Parkinson's disease (PD) compared to healthy controls, indicating its potential as a biomarker for neurodegeneration.

While [18F]AV-1451 demonstrated differences in binding between healthy individuals and those with parkinsonisms, further research is needed to confirm its effectiveness in imaging neurodegeneration across various forms of Parkinson's disease and related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]AV-1451 binding to neuromelanin in the substantia nigra in PD and PSP. Coakeley, S., Cho, SS., Koshimori, Y., et al.[2022]

The deuterated tracer D6-[18F]FP-(+)-DTBZ ([18F]9) was successfully optimized for production, achieving high radiochemical purity (>99%) and yield (38.7% decay corrected) using a simplified solid-phase extraction method.

This new imaging agent targets the vesicular monoamine transporter 2 (VMAT2) in the brain, making it a promising tool for diagnosing Parkinson's disease through PET imaging, with no significant differences in performance between different purification methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VMAT2 imaging agent, D6-[18F]FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and characterization. Zhao, R., Zha, Z., Yao, X., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10663012/

[18F]DPA-714 PET Imaging in the Presurgical Evaluation of ... [18F]DPA-714 PET seems to be more effective than [18F]FDG PET in revealing ... Increased microglial activation in patients with Parkinson disease using [18F]- ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32206840/

[18F]-DPA-714 PET as a specific in vivo marker of early ... Our study showed that in vivo PET study with [ 18 F]-DPA-714 is a selective and reliable biomarker of microglial activation and could be used to study ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0166432822004430

PET imaging in animal models of Parkinson's disease Oh et al. reported that microgliosis ([18F]DPA-714) was accompanied by increased levels of DAT (β-[18F]FP-CIT) and mGluR5 ([18F]FPEB) in the ...

4. ppmi-info.org ppmi-info.org/sites/default/files/docs/PPMI%20019%20DPA-714%20PET%20Imaging%20Study%20Protocol%20v1.1_27_Sep2023.pdf

Longitudinal TSPO PET imaging with [18F]DPA-714 in ... [18F]DPA-714, a 18Fluorine-labelled tracer, is proposed for this study due to its demonstrated high affinity for Translocator protein (TSPO) ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0969805111002459

Initial evaluation in healthy humans of [ 18 F]DPA-714, a ... This initial study in humans shows that [ 18 F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11403348/

Brain and Systemic Inflammation in De Novo Parkinson's ... Increased microglial activation in patients with Parkinson disease using [(18)F]‐DPA714 TSPO PET imaging. ... data identifies six new risk loci for Parkinson's ...

7. withpower.com withpower.com/trial/phase-2-parkinson-disease-2-2018-b052d

PET Scan with DPA-714 for Parkinson's Disease The safety of [18F]DPA-714 has been studied in nonhuman primates and patients with Parkinson's disease, showing its use in imaging without reported adverse ...

8. sciencedirect.com sciencedirect.com/science/article/am/pii/S096980432400085X

Automated radiosynthesis of [18F]DPA-714 on a ... Increased microglial activation in patients with Parkinson disease using. [18F]-DPA714 TSPO PET imaging Parkinsonism and Related Disorders 82, 29-36. Lin, Q ...