Brain Imaging for Post-Heart Attack Inflammation

Overseen By Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Pregnancy, Dementia, Major depression, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

6 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to see if positron emission tomography and magnetic resonance imaging (PET/MRI) with an investigational drug called \[18F\]DPA-714 will show inflammation in the brain after a heart attack. This study may help physicians and researchers better understand the role of brain inflammation in heart disease and develop new treatments to protect the brain.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug [18F]DPA-714 for imaging inflammation after a heart attack?

[18F]DPA-714 has been shown to effectively visualize inflammation in conditions like rheumatoid arthritis and stroke by targeting a protein that increases during inflammation. This suggests it could be useful for imaging inflammation after a heart attack as well. ^{1 2 3 4 5}

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

The safety of [18F]DPA-714 has been evaluated in preclinical studies, showing it is used to visualize inflammation in the brain without reported adverse effects in animal models. However, specific human safety data is not provided in the available research. ^{2 3 4 6 7}

How does this drug differ from other treatments for post-heart attack inflammation?

This drug uses a PET imaging tracer called [18F]DPA-714 to detect inflammation in the brain by targeting a protein associated with neuroinflammation. Unlike other treatments, it allows for non-invasive visualization of inflammation, which can help in monitoring the inflammatory response and evaluating treatment efficacy. ^{2 3 8 9 10}

Eligibility Criteria

This trial is for adults over 21 who've had a recent heart attack treated with PCI or are undergoing elective PCI. They must speak English, have at least an 8th-grade education, and be genetically predisposed to brain inflammation after a heart attack. People can't join if they're pregnant, breastfeeding, have serious health issues that could affect participation, history of severe head injury, major depression or dementia.

Inclusion Criteria

I am admitted to UAB Hospital for a severe heart attack and treated with PCI, or I am undergoing elective PCI.

I am 21 years old or older.

Participation in UAB IRB protocol 'Neuroinflammation After Acute Myocardial Infarction' (IRB-300002751, PI Lazar)

Exclusion Criteria

I have had heart bypass surgery in the past.

You have had a serious head injury that caused you to lose consciousness for more than 30 minutes or have a seizure.

I have had a heart attack before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET/MRI imaging to measure neuroinflammation using the investigational drug [18F]DPA-714

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• [18F]DPA-714

Trial Overview The study tests whether PET/MRI scans using the investigational drug [18F]DPA-714 can detect brain inflammation following a heart attack. This research aims to understand how heart disease affects the brain and may lead to new protective treatments.

Participant Groups

Group I: undergoing elective percutaneous coronary intervention Experimental Treatment 1 Intervention

Group II: Recent Myocardial Infarction Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

In a mouse model of stroke, treatment with AMD3100 significantly reduced neuroinflammation, as indicated by decreased TSPO levels measured through PET imaging, suggesting its potential as an anti-inflammatory therapy.

The study utilized a combination of in vivo PET scans and ex vivo histological analysis to confirm the effectiveness of AMD3100 in reducing inflammation, demonstrating the utility of TSPO-targeted imaging in evaluating treatment efficacy after ischemic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(18)F]DPA-714 PET imaging of AMD3100 treatment in a mouse model of stroke. Wang, Y., Yue, X., Kiesewetter, DO., et al.[2021]

The new radiotracer [18F]F-DPA was successfully synthesized and showed a high radiochemical purity of over 99%, indicating its potential for reliable use in imaging neuroinflammation.

In comparison to the related radiotracer [18F]DPA-714, [18F]F-DPA demonstrated a significantly higher stability in vivo, with 93.5% of the radioactivity remaining unchanged in the brain, suggesting it may be more effective for imaging neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats. Keller, T., Krzyczmonik, A., Forsback, S., 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]

References

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

PET Imaging of Neuroinflammation Using [11C]DPA-713 in a Mouse Model of Ischemic Stroke. [2018]

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

[(18)F]DPA-714 PET imaging of AMD3100 treatment in a mouse model of stroke. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Optimised GMP-compliant production of [18F]DPA-714 on the Trasis AllinOne module. [2021]

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

Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats. [2023]

5. England pubmed.ncbi.nlm.nih.gov

[¹⁸F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

KETO[18F]FDG -VAP-P1: In vivo studies of a potential PET radiotracer for diagnosis of inflammation. [2023]

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

Detection of neuroinflammation before selective neuronal loss appearance after mild focal ischemia using [18F]DPA-714 imaging. [2020]

9. Australia pubmed.ncbi.nlm.nih.gov

Longitudinal PET imaging of muscular inflammation using 18F-DPA-714 and 18F-Alfatide II and differentiation with tumors. [2021]

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

Comparison of high and low molar activity TSPO tracer [18F]F-DPA in a mouse model of Alzheimer's disease. [2021]