[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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the relationship between brain inflammation and carotid artery disease, a condition affecting the arteries that supply blood to the brain. It employs a special imaging technique with a tracer called [18F]DPA-714 (a radiolabeled imaging agent) to identify differences in brain inflammation between individuals with severe and mild artery narrowing. Participants must have a diagnosis of asymptomatic carotid artery disease and be part of a related study. Those with severe narrowing may join the "Critical Stenosis Group," while those with mild narrowing might join the "Non-Critical Stenosis Group." 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.

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 prior data suggests that [18F]DPA-714 is safe for imaging in carotid artery disease?

Research has shown that [18F]DPA-714, a PET imaging tracer, is generally safe for humans. This tracer binds well to a protein called TSPO, which helps measure inflammation in the brain and other areas. Previous studies did not find any major side effects or serious problems from its use. This suggests the tracer is safe, although testing remains in the early stages. As this trial is in the first phase, the main goal is to confirm safety and identify any possible side effects, meaning the treatment is still under careful evaluation for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [18F]DPA-714 imaging for carotid artery disease because it offers a new way to visualize inflammation in the arteries, which is key in understanding the progression of the disease. Unlike current treatments that focus primarily on managing symptoms and reducing risk factors, [18F]DPA-714 targets the inflammation itself by using a radiotracer that binds to specific proteins involved in the inflammatory process. This innovative approach could help in the early detection and better management of carotid artery disease by providing clearer insights into the disease's activity within the arteries.

What evidence suggests that [18F]DPA-714 is effective for imaging neuroinflammation in carotid artery disease?

Research has shown that [18F]DPA-714 is a promising tool for imaging brain inflammation. In earlier studies, this PET tracer effectively attached to TSPO, a protein linked to brain inflammation. Animal studies found that [18F]DPA-714 had less unwanted binding compared to older tracers, making it more reliable. Initial human tests also showed it was stable and spread well in the body. In this trial, [18F]DPA-714 will help detect inflammation in carotid artery disease, providing insights into the condition. Participants will be divided into two groups: one with critical asymptomatic carotid stenosis and another with non-critical asymptomatic carotid stenosis. ^{2 3 4 6 7}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-1-carotid-artery-diseases-5-2022-c02fe

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

2. clinicaltrial.be clinicaltrial.be/en/details/32802?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Neuroinflammation in Asymptomatic Carotid Artery Disease This clinical imaging substudy will use the small molecule translocator protein (TSPO) ligand, Fludeoxyglucose(18F)-labeled DPA-714, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40441893/

Whole-Body [18F]DPA-714 Kinetic Assessment Using PET ... 18 F]DPA-714 kinetics were studied by nonlinear regression fitting of 1- and 2-tissue-compartment models with an additional blood volume parameter to the time- ...

4. researchgate.net researchgate.net/publication/270004269_In_vivo_imaging_and_characterization_of_18FDPA-714_a_potential_new_TSPO_ligand_in_mouse_brain_and_peripheral_tissues_using_small-animal_PET

In vivo imaging and characterization of [18F]DPA-714, a ... According to several animal studies, [ 18 F]DPA-714 is better for PET imaging than [ 11 C]PK11195, due to its low nonspecific binding in the brain and the ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22172392/

Initial evaluation in healthy humans of [18F]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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05238961?cond=Asymptomatic%20Diseases&aggFilters=status:rec&viewType=Table&rank=4

Neuroinflammation in Asymptomatic Carotid Artery ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 ... The positron emission tomography (PET) tracer [18F]DPA-714 binds to the 18 ...

7. 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) ...