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

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.