PET-MR Imaging of Natriuretic Peptide Receptor C (NPR-C) in Carotid Atherosclerosis With 64Cu-NODAGA-CANF (Multisite)

October 29, 2026 updated by: Washington University School of Medicine

PET-MR Imaging of Natriuretic Peptide Receptor C (NPR-C) in Carotid Atherosclerosis With 64Cu-NODAGA-CANF

The goal of this clinical trial is to evaluate the feasibility of imaging atherosclerosis by 64Cu-NODAGA-CANF PET-MR in a pilot study of patients with asymptomatic carotid artery stenosis (ACAS). The main question it aims to answer is:

Can 64Cu-NODAGA-CANF PET detect carotid atherosclerosis in patients with ACAS?

Uptake of 64Cu-NODAGA-CANF as measured by PET-MR will also be correlated to anatomic features of plaque on MRI, outcomes for patients treated with optimal medical therapy (OMT) alone or OMT and carotid endarterectomy (CEA) surgery, and tissue measurements for patients undergoing CEA surgery. The ability of 64Cu-NODAGA-CANF to risk stratify ACAS patients treated with OMT alone with respect to patient outcomes will be determined.

Participants will

  • Receive a single intravenous (IV) administration of 64Cu-NODAGA-CANF followed by dynamic PET-MR imaging for up to 60 minutes and a second optional scan between 1-4 hours post-injection.
  • Undergo physical examinations, vital sign measurements, and blood and urine collection for clinical laboratory tests.
  • Undergo standard of care treatment with either OMT alone or OMT and CEA surgery.
  • Be evaluated with phone interviews 48-72 hours (2-3 days) after discharge and every 3 months (+/- 5 days) to assess for ipsilateral ischemic cerebrovascular event (transient ischemic attack (TIA), stroke) or remote ipsilateral carotid intervention.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a Phase 1, multicenter, open-label baseline controlled imaging study designed to assess whether 64Cu-NODAGA-CANF PET-MR can detect carotid atherosclerosis in patients with ACAS. A total of 30 subjects, both men and women (≥18 years of age), will be recruited at Washington University and Cedars Sinai, with approximately 25 patients recruited at Washington University and approximately 5 patients recruited at Cedars Sinai. Patients will receive a single intravenous (IV) bolus injection of 8-10 mCi of the investigational radiotracer 64Cu-NODAGA-CANF followed by dynamic PET-MR imaging for up to 60 minutes and a second optional scan between 1-4 hours post-injection. Patients will undergo 64Cu-NODAGA-CANF PET-MR imaging of both carotid arteries. Both carotid arteries will be imaged at the same time.

At the time of imaging, the investigators will record baseline medications to include any antiplatelet, statin, anti-hypertension, and diabetes medications (OMT), as well as basic risk factors and social history (e.g. diabetic, hypertensive, smoker, hypercholesterolemia). A physical examination will be performed at screening and prior to discharge. Vital signs will be obtained at baseline pre-injection, post-injection following each imaging session, and prior to discharge. Blood will be drawn at screening or baseline and prior to discharge to assess for interval change in serum chemistries and complete blood count. Urine will be collected at screening or baseline and prior to discharge to assess for interval change in urinalysis results. Blood samples will be obtained from all subjects at Washington University for radiolabeled metabolite analysis. Two-mL blood samples will be obtained at screening/baseline pre-injection and at 5 minutes and 30 minutes post 64Cu-NODAGA-CANF injection.

Telephone follow-up will occur within 48-72 hours (2-3 days) after discharge and every 3 months (+/- 5 days) to assess for ipsilateral ischemic cerebrovascular event (transient ischemic attack (TIA), stroke) or remote ipsilateral carotid intervention.

We hope to demonstrate differences in PET SUV (Standardized Uptake Value) in the significantly atherosclerotic artery in comparison to the PET SUV in the artery that is not significantly diseased.

We will also determine whether PET SUV of 64Cu-NODAGA-CANF correlates to anatomic features of plaque on MRI. The presence and volumes of various plaque components including lipid pool, fibrous cap, and intraplaque hemorrhage will be determined from the MR images. We will determine the ability of 64Cu-NODAGA-CANF to risk stratify ACAS patients treated with OMT alone with respect to patient outcomes. PET signal will be assessed as a marker of risk for event or progression to CEA surgery in comparison to anatomic features of vulnerable plaque on MRI, with the goal of determining 64Cu-NODAGA-CANF PET signal above which suggests ACAS at higher risk for causing stroke. In patients who undergo CEA surgery, the ex vivo post-operative plaque specimen will be collected and PET uptake will be correlated to tissue measurements including the American Heart Association classifications of atherosclerosis and tissue presence of NPR-C.

Study Type

Observational

Enrollment (Estimated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
        • Contact:
        • Principal Investigator:
          • Yibin Xie, PhD
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Pamela K. Woodard, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Individuals ≥18 years of age with asymptomatic carotid artery stenosis.

Description

Inclusion Criteria:

  • Adults, 18 years of age or older.
  • Asymptomatic carotid artery stenosis patients who have undergone carotid Doppler/ultrasound imaging or other carotid imaging which have demonstrated a ≥ 60% diameter carotid artery stenosis.
  • The treating surgeon has planned either treatment with optimal medical therapy (OMT) alone or OMT and carotid endarterectomy (CEA) surgical intervention.

Exclusion Criteria:

  • Inability to receive and sign informed consent.
  • Patients with an unstable clinical condition that in the opinion of the Sponsor-Investigator or designee precludes participation in the study.
  • Inability to tolerate up to 60 minutes in a supine position with arms down at sides for PET-MR imaging.
  • Prior history of carotid endarterectomy (CEA) or carotid artery stent procedure on the ipsilateral side.
  • Past medical history of transient ischemic attack (TIA) or stroke within the last 6 months.
  • Unwilling to comply with study procedures and/or unable to be available for the duration of the study outlined in the protocol.
  • Claustrophobia or other preventing condition that has previously or would interfere with completion of imaging as outlined in the protocol.
  • Participation in another research study with an investigational drug, including a diagnostic or therapeutic radiopharmaceutical, currently or within the last year.
  • Contraindications to MR imaging (pacemaker, brain aneurysm clips, shrapnel, claustrophobia, etc.).
  • Currently pregnant or lactating. All female subjects of childbearing potential must have a documented negative pregnancy test (serum or urine hCG) performed within 24 hours immediately prior to the administration of 64Cu-NODAGA-CANF or documented post-menopausal defined as the cessation of menses for ≥ 12 months or documentation of having a bilateral oophorectomy and/or hysterectomy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: COHORT
  • Time Perspectives: PROSPECTIVE

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients treated with Optimal Medical Therapy (OMT) alone

Asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler or other carotid imaging with ≥ 60% diameter stenosis who are clinically referred for OMT alone.
Drug: 64Cu-NODAGA-CANF

Patients will receive a single intravenous (IV) injection of 8-10 mCi of 64Cu-NODAGA-CANF for PET-MR imaging at the imaging visit.
Patients treated with OMT and carotid endartarectomy (CEA)

Asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler or other carotid imaging with ≥ 60% diameter stenosis who are clinically referred for OMT and CEA.
Drug: 64Cu-NODAGA-CANF

Patients will receive a single intravenous (IV) injection of 8-10 mCi of 64Cu-NODAGA-CANF for PET-MR imaging at the imaging visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of 64Cu-NODAGA-CANF PET SUV (Standardized Uptake Value) between the atherosclerosis of the target diseased carotid artery and the non-diseased contralateral carotid artery or non-diseased vertebral artery
Time Frame: Up to 4 hours post-injection of 64Cu-NODAGA-CANF

PET uptake of 64Cu-NODAGA-CANF will be quantified as SUV. For each subject, PET SUV will be measured in the atherosclerosis of the diseased carotid artery and in a region of non-disease in the contralateral carotid artery, or if the contralateral carotid is completely diseased, a portion of non-diseased vertebral artery. Mean SUV in the atherosclerosis of the diseased carotid arteries will be compared to mean SUV in the non-diseased contralateral carotid arteries or non-diseased vertebral arteries.
Up to 4 hours post-injection of 64Cu-NODAGA-CANF

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of 64Cu-NODAGA-CANF PET uptake to American Heart Association (AHA) stage of atherosclerotic plaque as determined by MRI
Time Frame: Up to 4 hours post-injection of 64Cu-NODAGA-CANF

Patients with carotid atherosclerosis will be imaged with 64Cu-NODAGA-CANF PET-MR. MRI is acquired simultaneously with 64Cu-NODAGA-CANF PET. MR images will be evaluated for AHA plaque stage. PET uptake of 64Cu-NODAGA-CANF will be quantified as SUV. PET signal (SUV) will be compared between patients with different AHA stages of atherosclerotic plaque.
Up to 4 hours post-injection of 64Cu-NODAGA-CANF
Correlation of 64Cu-NODAGA-CANF PET uptake to absence or presence of atherosclerosis as determined by MRI
Time Frame: Up to 4 hours post-injection of 64Cu-NODAGA-CANF

Patients with carotid atherosclerosis will be imaged with 64Cu-NODAGA-CANF PET-MR. MRI is acquired simultaneously with 64Cu-NODAGA-CANF PET. MR images will be evaluated for absence or presence of atherosclerosis. PET uptake of 64Cu-NODAGA-CANF will be quantified as SUV. PET signal (SUV) will be compared between patients with absence or presence of atherosclerosis.
Up to 4 hours post-injection of 64Cu-NODAGA-CANF
Correlation of 64Cu-NODAGA-CANF PET uptake to absence or presence of lipid core as determined by MRI
Time Frame: Up to 4 hours post-injection of 64Cu-NODAGA-CANF

Patients with carotid atherosclerosis will be imaged with 64Cu-NODAGA-CANF PET-MR. MRI is acquired simultaneously with 64Cu-NODAGA-CANF PET. MR images will be evaluated for absence or presence of lipid core. PET uptake of 64Cu-NODAGA-CANF will be quantified as SUV. PET signal (SUV) will be compared between patients with absence or presence of lipid core.
Up to 4 hours post-injection of 64Cu-NODAGA-CANF
Correlation of 64Cu-NODAGA-CANF PET uptake to absence or presence of hemorrhage as determined by MRI
Time Frame: Up to 4 hours post-injection of 64Cu-NODAGA-CANF

Patients with carotid atherosclerosis will be imaged with 64Cu-NODAGA-CANF PET-MR. MRI is acquired simultaneously with 64Cu-NODAGA-CANF PET. MR images will be evaluated for absence or presence of hemorrhage. PET uptake of 64Cu-NODAGA-CANF will be quantified as SUV. PET signal (SUV) will be compared between patients with absence or presence of hemorrhage.
Up to 4 hours post-injection of 64Cu-NODAGA-CANF
Correlation of 64Cu-NODAGA-CANF PET uptake to outcomes
Time Frame: Up to 4 years following PET-MR imaging

PET uptake of 64Cu-NODAGA-CANF will be quantified as SUV. We will determine the ability of 64Cu-NODAGA-CANF to risk stratify ACAS patients with respect to patient outcomes. Patients will be contacted every 3 months after PET-MR imaging to assess for interval ipsilateral ischemic cerebrovascular event (transient ischemic attack (TIA), stroke) or remote ipsilateral carotid intervention. PET signal will be assessed as a marker of risk for event or progression to CEA surgery. 64Cu-NODAGA-CANF PET signal (SUV) will compared between patients who experienced or did not experience an ipsilateral ischemic cerebrovascular event (TIA, stroke) or remote ipsilateral carotid intervention (carotid endarterectomy (CEA) surgery or stent placement).
Up to 4 years following PET-MR imaging
Correlation of 64Cu-NODAGA-CANF PET uptake to American Heart Association (AHA) stage of atherosclerotic plaque as determined by histology on ex vivo tissue specimens for patients undergoing CEA surgery
Time Frame: Immediately after surgery

PET uptake of 64Cu-NODAGA-CANF will be quantified as SUV. In patients who undergo CEA, the ex vivo post-operative plaque specimen will be collected. Tissue measurements will include American Heart Association (AHA) plaque stage as an indicator of plaque vulnerability. AHA stage of atherosclerotic plaque will be determined by assessment of hematoxylin and eosin (H&E), Verhoeff-Van Gieson (VVG), and pentachrome stained specimens. 64Cu-NODAGA-CANF PET signal (SUV) obtained from images pre-surgery will be compared between patients with different AHA stages of atherosclerotic plaque on the surgical tissue specimen.
Immediately after surgery
Correlation of 64Cu-NODAGA-CANF PET uptake to expression of targeted receptor, NPR-C, by immunohistochemistry on ex vivo tissue specimens for patients undergoing CEA surgery
Time Frame: Immediately after surgery

PET uptake of 64Cu-NODAGA-CANF will be quantified as SUV. In patients who undergo CEA, the ex vivo post-operative plaque specimen will be collected. Tissue measurements will include expression of NPR-C by immunohistochemistry. 64Cu-NODAGA-CANF PET signal (SUV) obtained from images pre-surgery will be correlated to expression of NPR-C on the surgical tissue specimen.
Immediately after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Cedars-Sinai Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 18, 2026

Primary Completion (Estimated)

May 31, 2027

Study Completion (Estimated)

May 31, 2027

Study Registration Dates

First Submitted

October 29, 2026

First Submitted That Met QC Criteria

October 29, 2026

First Posted (Actual)

November 4, 2026

Study Record Updates

Last Update Posted (Actual)

November 4, 2026

Last Update Submitted That Met QC Criteria

October 29, 2026

Last Verified

October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202609211
  • R01HL159803 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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