PET Imaging for Parkinson's Disease

Overseen by Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Alabama at Birmingham

Disqualifiers: High radiation exposure, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The overall goal of this protocol is to investigate \[18F\]DPA-714 binding in prodromal and early manifest Parkinson's Disease (PD) and to determine the baseline and change from baseline in \[18F\]DPA-714 binding in PD participants during a 24-month interval. Primary Objectives * To compare \[18F\]DPA-714 binding in prodromal and manifest PD and healthy volunteers. * To determine the longitudinal change in \[18F\]DPA-714 during a 24-month interval for prodromal and early initially untreated PD participants. Secondary Objectives * To evaluate the correlation between baseline \[18F\]DPA-714 and PPMI clinical and biomarker outcomes. * To evaluate the correlation between the longitudinal change of \[18F\]DPA-714 and PPMI clinical and biomarker outcomes * To acquire safety data following injection of \[18F\]DPA-714

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.

Is [18F]DPA714 safe for use in humans?

The research does not provide specific safety data for [18F]DPA714 in humans, but it has been used in studies to monitor brain inflammation in conditions like Alzheimer's disease and Parkinson's disease, suggesting it is considered safe enough for research purposes. ^{1 2 3 4 5}

How does PET imaging differ from other treatments for Parkinson's disease?

PET imaging for Parkinson's disease is unique because it uses special imaging techniques to visualize brain activity and inflammation, helping to diagnose and monitor the disease, rather than directly treating symptoms like traditional medications. ^{1 6 7 8 9}

Research Team

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

David Standaert, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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

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

Able to provide informed consent

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

Trial Timeline

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

Treatment Details

Interventions

• [F-18]DPA714 (Virus Therapy)

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.

Participant Groups

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+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

Michael J. Fox Foundation for Parkinson's Research

Collaborator

Trials

117

Recruited

537,000+

Deborah W. Brooks

Michael J. Fox Foundation for Parkinson's Research

Chief Executive Officer since 2021

AB in Economics from the College of William and Mary, MBA from the Tuck School at Dartmouth College, MS in Marital and Family Therapy from Northwestern University

Mark Frasier

Michael J. Fox Foundation for Parkinson's Research

Chief Medical Officer since 2006

PhD in Pharmacology from Loyola University Chicago

Findings from Research

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 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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

[18F]AV-1451 binding to neuromelanin in the substantia nigra in PD and PSP. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

PET Imaging for Dynamically Monitoring Neuroinflammation in APP/PS1 Mouse Model Using [18F]DPA714. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Imaging of dopamine transporters in Parkinson disease: a meta-analysis of 18 F/123 I-FP-CIT studies. [2021]

5. Japan 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. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Molecular Imaging of Neurodegenerative Parkinsonism. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

VMAT2 imaging agent, D6-[18F]FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and characterization. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Clinical Significance of F-18 FP-CIT Dual Time Point PET Imaging in Idiopathic Parkinson's Disease. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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