PET Scan with DPA-714 for Parkinson's Disease

Recruiting in Palo Alto (17 mi)

Overseen by Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Alabama at Birmingham

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

The primary objective of this substudy is to measure the concentration and the regional brain distribution of activated brain microglia/macrophages using the PET ligand \[18F\]DPA-714 in participants enrolled in the UAB Innate and Adaptive Immunity in Parkinson's Disease (Clinical Research Core) and Longitudinal \[18F\]DPA-714 Imaging in a Parkinson Disease Cohort studies. The PET tracer \[18F\]DPA-714 binds to the 18 kDa translocator protein (TSPO, also known as the peripheral benzodiazepine receptor) in the mitochondria of activated microglia/macrophages and provides a non-invasive measure of neuroinflammation. The amount and distribution of \[18F\]DPA-714 in the brain will be correlated to clinical data acquired through the separate ongoing UAB Innate and Adaptive Immunity in Parkinson Disease (Clinical Research Core) and Longitudinal \[18F\]DPA-714 Imaging in a Parkinson Disease Cohort studies. The primary objective of this study is to determine if patients with PD have higher levels of neuroinflammation than healthy controls as measured with \[18F\]DPA-714-PET/MRI.

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 data supports the effectiveness of the treatment DPA-714-PET/MRI for Parkinson's Disease?

The use of PET imaging with 18F-DOPA, a similar tracer to 18F-DPA-714, has been shown to be effective in diagnosing and understanding Parkinson's Disease by highlighting brain areas affected by the disease. This suggests that DPA-714-PET/MRI might also be useful in providing valuable insights into Parkinson's Disease. ^{1 2 3 4 5}

Is [18F]DPA-714 safe for use in humans?

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 effects. However, specific safety data in humans for this compound is limited, and further studies are needed to confirm its safety profile. ^{6 7 8 9 10}

How does the PET Scan with DPA-714 treatment for Parkinson's Disease differ from other treatments?

The PET Scan with DPA-714 is unique because it uses a specific imaging technique to visualize brain changes in Parkinson's Disease, which can help in early diagnosis and monitoring of the disease's progression. Unlike traditional treatments that focus on symptom management, this approach aims to provide a clearer understanding of the disease's impact on the brain. ^{2 11 12 13 14}

Research Team

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• DPA-714-PET/MRI (PET Tracer)

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.

Participant Groups

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+

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

Findings from Research

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]

(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]

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 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 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]

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]

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]

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]

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

Amino Acid PET Imaging with 18F-DOPA in the evaluation of Pediatric Brain Tumors. [2022]

2. Greece pubmed.ncbi.nlm.nih.gov

Current status and future challenges of brain imaging with (18)F-DOPA PET for movement disorders. [2016]

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

The role of high-field magnetic resonance imaging in parkinsonian disorders: Pushing the boundaries forward. [2022]

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

Initial Results of a Phase 2 Trial of 18F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma. [2023]

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. England pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

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

8. Germany 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. [2023]

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

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

10. Germany 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. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Recent advances in PET imaging for evaluation of Parkinson's disease. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT-a clinical comparison. [2020]

13. Switzerland pubmed.ncbi.nlm.nih.gov

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

14. Germany pubmed.ncbi.nlm.nih.gov

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