[18F]DPA-714 Imaging for Carotid Artery Disease

Overseen By Evan Hudson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Pregnancy, Prior stroke, Major depression, Dementia, 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: Unknown

20 Participants Needed

Trial Summary

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

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug [18F]DPA-714 for carotid artery disease?

While there is no direct evidence for [18F]DPA-714, similar imaging agents like [18F]FDG have shown potential in identifying vulnerable carotid plaques, which are linked to stroke risk. This suggests that [18F]DPA-714 might also help in assessing carotid artery disease by highlighting areas of inflammation or vulnerability. ^{1 2 3 4 5}

How does [18F]DPA-714 imaging differ from other treatments for carotid artery disease?

[18F]DPA-714 imaging is unique because it uses a PET scan to visualize inflammation in the carotid arteries, which can help identify vulnerable plaques that might lead to strokes. This approach is different from traditional treatments that focus on reducing plaque size or improving blood flow, as it provides detailed information about plaque stability and inflammation. ^{1 2 4 6 7}

What is the purpose of this trial?

This clinical imaging substudy will use the small molecule translocator protein (TSPO) ligand, Fludeoxyglucose(18F)-labeled DPA-714, to compare neuroinflammation in individuals with high or low grade asymptomatic carotid artery stenosis (aCAD) who are participating in the separate Neuroinflammation in Asymptomatic Carotid Artery Disease study lead by Dr. Ron Lazar (IRB-300007806). The positron emission tomography (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.

Research Team

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults with asymptomatic carotid artery disease, either with over 70% stenosis or less than 40%, depending on the group. Participants must be fluent in English, have at least an 8th-grade education, and show high affinity binding for TSPO ligands. Pregnant women, individuals with major depression, dementia, previous strokes or head injuries are excluded.

Inclusion Criteria

I have a genetic marker linked to better outcomes in carotid stenosis treatment.

I am scheduled for a procedure to open my narrowed neck artery in more than 14 days.

I am 18 or older with non-critical, symptom-free carotid artery narrowing.

Exclusion Criteria

My genetic test shows low or mixed-affinity for TSPO ligands.

I have had a procedure to improve blood flow to my heart.

Serious medical comorbidity that, based on the judgement of the principal investigator, may interfere with study participation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET imaging using the TSPO ligand, Fludeoxyglucose(18F)-labeled DPA-714, to measure neuroinflammation

48 hours

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• [18F]DPA-714

Trial Overview [18F]DPA-714 PET tracer is being tested to measure neuroinflammation in patients with different severities of asymptomatic carotid artery disease. The study involves comparing brain scans from two groups: one with critical stenosis and another with non-critical stenosis.

Participant Groups

Group I: Cohort 2 - Controls-Non-Critical Asymptomatic Carotid Stenosis Group Experimental Treatment 1 Intervention

\<40% carotid stenosis No planned revascularization

Group II: Cohort 1 - Critical Asymptomatic Carotid Stenosis Group Experimental Treatment 1 Intervention

Critical Stenosis Group: Diagnosis of Asymptomatic Carotid Artery Disease (aCAD) with \>70% stenosis or peak systolic velocity on duplex ultrasound (DUS) ≥ 230 cm/s plus computed tomography angiography (CTA) or magnetic resonance angiography (MRA) confirmation.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

Carotid arteries that experienced recent ischemic events showed significantly higher uptake of the PET tracer 18F-FDG compared to asymptomatic arteries, indicating a potential link between increased tracer uptake and plaque vulnerability.

While the findings suggest that both 18F-FDG and 18F-NaF may be useful in evaluating carotid plaque and predicting ischemic events, the significant variability in results means more research is needed to confirm these associations and their clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carotid Plaque Positron Emission Tomography Imaging and Cerebral Ischemic Disease. Chaker, S., Al-Dasuqi, K., Baradaran, H., et al.[2020]

In a study of 18 stroke patients, FDG PET imaging was found to be more effective than NaF PET in detecting symptomatic carotid atherosclerosis, showing significantly higher uptake in symptomatic arteries compared to asymptomatic ones.

NaF PET uptake correlated with the degree of calcification in carotid atheroma, indicating that while it does not differentiate between symptomatic and asymptomatic conditions, it can reflect the overall calcification burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of 18F-Fluorodeoxyglucose and 18F-Fluoride Positron Emission Tomography in Korean Stroke Patients with Carotid Atherosclerosis. Kim, JM., Lee, ES., Park, KY., et al.[2022]

A 47-year-old male with mild internal carotid artery stenosis (45%) and familial hypercholesterolemia showed high uptake of FDG in carotid plaque, indicating inflammation and potential risk for ischemic events.

The case suggests that FDG PET imaging could be a valuable tool for identifying vulnerable carotid plaques and predicting stroke risk, even in patients with less severe stenosis, highlighting its potential role in clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18-fluorodeoxyglucose positron emission tomography may predict the outcome in patients with asymptomatic mild stenosis of internal carotid artery--case report. Motegi, H., Kuroda, S., Nakayama, N., et al.[2019]

Integrated (18)F-FDG PET/MDCT can identify differences in carotid plaques in patients with TIA/stroke, but significant differences were only observed in patients imaged within 38 days of their last symptoms, indicating a time-sensitive aspect to the imaging's effectiveness.

MDCT was able to detect larger vessel wall and lipid-rich necrotic core (LRNC) volumes in ipsilateral plaques compared to contralateral asymptomatic plaques, suggesting it may provide valuable information regardless of the timing of imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of integrated [18F] fluorodeoxyglucose positron-emission tomography/CT in identifying vulnerable carotid plaques. Kwee, RM., Truijman, MT., Mess, WH., et al.[2021]

In a study of 50 patients with symptomatic carotid atherosclerosis, (18)F-FDG PET showed weak correlations with CT and MRI findings, indicating that these imaging techniques may not reliably assess carotid plaque characteristics together.

CT and MRI measurements demonstrated moderate to strong correlations, particularly in mildly calcified plaques, suggesting that while they can complement each other, there is significant variability in their absolute measurements of plaque features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodality imaging of carotid artery plaques: 18F-fluoro-2-deoxyglucose positron emission tomography, computed tomography, and magnetic resonance imaging. Kwee, RM., Teule, GJ., van Oostenbrugge, RJ., et al.[2022]

In a study of 110 participants with acute neurovascular syndrome, 18F-NaF PET/MRI imaging revealed that culprit carotid arteries had significantly higher levels of plaque instability features, such as intraplaque hemorrhage and ulceration, compared to nonculprit arteries.

Higher uptake of 18F-NaF was associated with more severe plaque characteristics, including necrosis and calcification, indicating that this imaging technique could help identify high-risk plaques that may lead to strokes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-NaF PET/MRI for Detection of Carotid Atheroma in Acute Neurovascular Syndrome. Kaczynski, J., Sellers, S., Seidman, MA., et al.[2023]

In a study of 26 patients who had experienced a transient ischemic attack or minor stroke, 18F-fluoride PET/CT was found to effectively identify high-risk carotid plaques, showing increased uptake in culprit plaques compared to asymptomatic ones, which could help in better risk assessment for interventions.

While 18F-fluorodeoxyglucose showed some correlation with cardiovascular risk, it did not differentiate between culprit and non-culprit plaques as effectively as 18F-fluoride, highlighting the latter's superior ability to identify dangerous plaque characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-Fluoride and 18F-Fluorodeoxyglucose Positron Emission Tomography After Transient Ischemic Attack or Minor Ischemic Stroke: Case-Control Study. Vesey, AT., Jenkins, WS., Irkle, A., et al.[2021]

References

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

Carotid Plaque Positron Emission Tomography Imaging and Cerebral Ischemic Disease. [2020]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Analysis of 18F-Fluorodeoxyglucose and 18F-Fluoride Positron Emission Tomography in Korean Stroke Patients with Carotid Atherosclerosis. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Fluorine-18-fluorodeoxyglucose positron emission tomography may predict the outcome in patients with asymptomatic mild stenosis of internal carotid artery--case report. [2019]

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

Potential of integrated [18F] fluorodeoxyglucose positron-emission tomography/CT in identifying vulnerable carotid plaques. [2021]

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

Multimodality imaging of carotid artery plaques: 18F-fluoro-2-deoxyglucose positron emission tomography, computed tomography, and magnetic resonance imaging. [2022]

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

18F-NaF PET/MRI for Detection of Carotid Atheroma in Acute Neurovascular Syndrome. [2023]

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

18F-Fluoride and 18F-Fluorodeoxyglucose Positron Emission Tomography After Transient Ischemic Attack or Minor Ischemic Stroke: Case-Control Study. [2021]