PET Scan with DPA-714 for Parkinson's Disease

Overseen By Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Alabama at Birmingham

Disqualifiers: Low TSPO affinity, MRI/PET contraindication, others

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

Compensation: Varies

Number of Visits: 3

205 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates brain inflammation in people with Parkinson's Disease using a special imaging method called DPA-714-PET/MRI. The goal is to determine if individuals with Parkinson's have more brain inflammation than healthy individuals. Participants will be grouped into those with early Parkinson's and healthy controls for comparison. This trial suits those already enrolled in certain UAB Parkinson’s studies and who can undergo PET/MRI scans without issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to get a clear answer.

What prior data suggests that this PET scan is safe for Parkinson's Disease patients?

Research has shown that the PET tracer \[18F\]DPA-714 has been safely used in both animals and people with Parkinson's disease. In these studies, no side effects were reported from its use in brain imaging, suggesting that the tracer is generally safe for studying brain inflammation. However, safety can vary among individuals. It is important to discuss potential risks and benefits with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using DPA-714-PET/MRI for Parkinson's Disease because it offers a cutting-edge way to visualize brain inflammation, something standard treatments like Levodopa or dopamine agonists don't address. Unlike traditional methods that primarily focus on symptom relief, DPA-714-PET/MRI provides detailed information on neuroinflammation, which could lead to better understanding and management of the disease. This technique allows for a more precise diagnosis and monitoring of disease progression, potentially leading to breakthroughs in treatment strategies for Parkinson's Disease.

What evidence suggests that this PET scan method is effective for measuring neuroinflammation in Parkinson's disease?

Research has shown that \[18F\]DPA-714 is a promising tool for imaging brain inflammation in Parkinson's disease (PD). Studies have found that this PET tracer attaches to a protein in brain cells called TSPO, enabling doctors to visualize brain inflammation. Early findings suggest that \[18F\]DPA-714 effectively highlights inflammation in the early stages of PD. In previous studies with healthy individuals, the tracer showed good stability and distribution throughout the body, supporting its potential use in PD research. This trial will use \[18F\]DPA-714 to identify brain changes related to inflammation in Parkinson's disease, with different cohorts including healthy controls and individuals with early PD. ^{1 3 6 7 8}

Who Is on the Research Team?

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for participants already enrolled in the UAB Neuroinflammation in Parkinson's Disease study. It's specifically for those who can undergo PET/MRI scans and are not pregnant or at risk of pregnancy. Individuals must have a certain genetic profile (high or mixed affinity binder) that allows them to bind well with the imaging agent used.

Inclusion Criteria

Parkinson's Disease participant enrolled in UDALL Baseline Cohort. Baseline imaging to be completed no more than 6 years prior

Enrollment in either the UAB Innate and Adaptive Immunity in Parkinson Disease (Clinical Research Core) study or UAB Longitudinal [18F]DPA-714 Imaging in a Parkinson Disease Cohort study under the separate UAB-approved research protocols (IRB-300001745 and IRB-300011684 respectively, PI Yacoubian)

I am not pregnant or have been menopausal for over a year or am surgically sterilized.

Exclusion Criteria

Meets any exclusion criteria for the UAB Innate and Adaptive Immunity in Parkinson's Disease (Clinical Research Core) study or UAB Longitudinal [18F]DPA-714 Imaging in a Parkinson's Disease Cohort study

Inability to participate in the imaging studies due to severity of PD or other medical comorbidities

Contraindication to MRI and/or PET imaging

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo one-time DPA-714 PET/MRI imaging to measure neuroinflammation

1 day

1 visit (in-person)

Follow-up Imaging

67 PD participants from the baseline cohort receive follow-up DPA-714 PET/MRI imaging approximately 5 years after baseline imaging

5 years

1 visit (in-person)

Metabolite Analysis

Five PD participants undergo DPA-714 PET/MRI imaging, arterial line placement, and metabolite sampling

1 day

1 visit (in-person)

Long-term Follow-up

Participants are monitored for changes in neuroinflammation and correlation with clinical data over time

2 years

What Are the Treatments Tested in This Trial?

Interventions

• DPA-714-PET/MRI

Trial Overview The substudy is testing how a PET tracer called [18F]DPA-714 distributes and concentrates in the brain, which could indicate levels of neuroinflammation in Parkinson’s patients compared to healthy individuals. The tracer binds to proteins associated with inflammation in brain immune cells.

How Is the Trial Designed?

Group I: UDALL 5-year Follow-up Cohort Experimental Treatment 1 Intervention

n-67 from baseline early Parkinson's disease cohort

Group II: Metabolite Analysis Cohort Experimental Treatment 1 Intervention

n-5 from baseline early Parkinson's disease cohort

Group III: Baseline Cohort Healthy Controls, DPA-714-PET/MRI Experimental Treatment 1 Intervention

n-105

Group IV: Baseline Cohort Early Parkinson's Disease, DPA-714-PET/MRI Experimental Treatment 1 Intervention

n-100

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Parkinson's disease is characterized by the loss of dopamine-producing neurons in the brain, which disrupts movement regulation through two main dopamine pathways: the direct pathway (D(1) receptors) and the indirect pathway (D(2) receptors).

Positron emission tomography (PET) is an effective non-invasive imaging technique that can help evaluate Parkinson's disease and distinguish it from other similar disorders by using specific tracers to visualize dopamine activity in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in PET imaging for evaluation of Parkinson's disease. Sioka, C., Fotopoulos, A., Kyritsis, AP.[2021]

Amino-acid PET imaging, particularly using 18F-DOPA, is increasingly recommended alongside MRI for evaluating and managing brain tumors, as it provides valuable insights at various stages of treatment.

There is strong evidence supporting the use of 18F-DOPA in adults for brain tumor evaluations, and emerging data suggests its effectiveness in pediatric cases as well, highlighting its potential for broader clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino Acid PET Imaging with 18F-DOPA in the evaluation of Pediatric Brain Tumors. Djekidel, M., Alsadi, R., Bouhali, O., et al.[2022]

Modern MRI techniques, such as iron- and neuromelanin-sensitive imaging, have revealed important markers for diagnosing Parkinson's disease (PD) and tracking its progression, which were previously overlooked.

High-field (3T) and ultra high-field (7T) MRI can capture both structural and functional brain changes, aiding in the understanding of neurodegeneration and providing potential biomarkers for therapeutic trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of high-field magnetic resonance imaging in parkinsonian disorders: Pushing the boundaries forward. Lehericy, S., Vaillancourt, DE., Seppi, K., et al.[2022]

In a study involving 75 patients with glioblastoma, 18F-DOPA PET-guided dose-escalated radiation therapy (DERT) demonstrated a significant improvement in progression-free survival (PFS) for patients with unmethylated MGMT, achieving a PFS rate of 79.5% at 6 months.

The treatment was found to be safe, with only 13% of patients experiencing grade 3 central nervous system necrosis, which was effectively managed with bevacizumab, indicating a favorable safety profile for this innovative approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Results of a Phase 2 Trial of 18F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma. Laack, NN., Pafundi, D., Anderson, SK., et al.[2023]

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]

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]

The radioligand [(18)F]DPA-714 binds specifically to the translocator protein (TSPO) in the primate brain, with about 73% of its binding being specific, making it a valuable tool for studying neuroinflammation.

In a model of neurodegeneration induced by quinolinic acid, [(18)F]DPA-714 showed a significant increase in binding over time, correlating with microglial activation, indicating its potential for assessing neuroinflammatory responses in conditions like neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]DPA-714 PET imaging of translocator protein TSPO (18 kDa) in the normal and excitotoxically-lesioned nonhuman primate brain. Lavisse, S., Inoue, K., Jan, C., et al.[2022]

DAT imaging using the radiopharmaceutical [18F]FE-PE2I PET shows significant differences in dopamine transporter availability between patients with early-stage parkinsonian syndrome and healthy controls, indicating its strong diagnostic potential.

FE-PE2I PET provides diagnostic accuracy comparable to the commonly used FP-CIT SPECT, with high correlation in measurements of dopamine transporter availability, suggesting it is a reliable method for assessing dopaminergic deficits in early-stage parkinsonian disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT-a clinical comparison. Jakobson Mo, S., Axelsson, J., Jonasson, L., et al.[2020]

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]

(18)F-DOPA PET imaging is the most effective diagnostic tool for identifying Parkinson's disease (PD) and other movement disorders, as it can detect presynaptic dysfunction early in the disease process.

Fluorine-18-FDG PET can help differentiate between PD and other parkinsonian syndromes, while the combination of (18)F-DOPA PET with MRI may enhance early diagnosis capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status and future challenges of brain imaging with (18)F-DOPA PET for movement disorders. Calabria, FF., Calabria, E., Gangemi, V., et al.[2016]

The new PET imaging agent [18F]PR04.MZ shows excellent image quality for evaluating dopamine transporters in patients with movement disorders, particularly Parkinson's disease, based on a study involving six healthy subjects.

The biodistribution results indicate that [18F]PR04.MZ is primarily excreted through the liver and kidneys, with a favorable dosimetry profile, making it suitable for larger clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-body biodistribution and radiation dosimetry of [18F]PR04.MZ: a new PET radiotracer for clinical management of patients with movement disorders. Lehnert, W., Riss, PJ., Hurtado de Mendoza, A., et al.[2023]

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]

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]

Citations

1. 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) ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37134001/

Revealed by PET-MRI Imaging by [18F]DPA-714 Targeting ... [ 18 F]DPA-714 appeared to be a potential PET tracer for imaging the microglia-mediated neuroinflammation in the early stage of PD.

3. 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 ...

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

PET Scan with DPA-714 for Parkinson's Disease The primary objective of this study is to determine if patients with PD have higher levels of neuroinflammation than healthy controls as measured with \[18F\] ...

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

[18F]DPA-714 PET Imaging in the Presurgical Evaluation of ... In this study, when [18F]FDG PET failed to detect the EZ, TSPO PET was found to be very effective in detecting an anomaly (100% in visual analysis, 70.8% in ROI ...

6. clinicaltrial.be clinicaltrial.be/en/details/427708?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Longitudinal TSPO PET Imaging with [18F]DPA-714 in PPMI (... 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 ...

7. protocols.io protocols.io/view/longitudinal-tspo-pet-imaging-with-18f-dpa-714-in-dccw2sxe

Longitudinal TSPO PET imaging with [18F] DPA-714 in ... The overall goal of this protocol is to investigate [18F]DPA-714 binding in prodromal and early manifest Parkinson's Disease (PD) and to ...

8. pubs.acs.org pubs.acs.org/doi/abs/10.1021/acschemneuro.3c00202

Revealed by PET-MRI Imaging by [18F]DPA-714 Targeting ... 18 F]DPA-714 appeared to be a potential PET tracer for imaging the microglia-mediated neuroinflammation in the early stage of PD.