CANF-Comb-II PET-MR in Atherosclerosis Multisite

This is an NIH-funded, Phase II, multicenter, open-label patient outcomes imaging study. Patients will undergo carotid PET/MRI after intravenous injection of 2-6 milliCuries (mCi) of the FDA Exploratory Investigational New Drug (eIND)-approved nanoparticle PET radiotracer (64Cu-C-type atrial natriuretic factor (CANF)-Comb). A total of 80 subjects will be recruited to this study. These subjects will be asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler or other carotid imaging ≥ 60% diameter stenosis. These patients will be asked to undergo a carotid PET/MRI at a single time point 12-24 hours after intravenous injection of the 64Cu-CANF-Comb radiotracer.

Based on promising results from a proof of concept study, the investigators have devised an imaging protocol to determine the ability of 64Cu-25%-CANF-Comb PET to risk stratify ACAS patients treated with optimal medical therapy (OMT) alone with respect to patient outcomes. In this observational study, 80 patients with ACAS ≥ 60% will undergo 64Cu-25%-CANF-Comb PET/MRI. Patients will be maintained on either OMT alone or receive OMT and carotid endarterectomy (CEA) as determined by their treating vascular surgeon prior to imaging.

A total of 80 subjects, both men and women (≥18 years of age), will be recruited at Washington University (WU) and Cedars Sinai, with approximately 59 patients recruited at WU and approximately 21 patients recruited at Cedars Sinai. Patients will be asked to undergo carotid PET/MRI after intravenous injection of 64Cu-25%-CANF-Comb. These 80 subjects will be asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler or other carotid imaging ≥ 60% diameter stenosis. These patients will be asked to undergo a carotid PET/MRI at a single time point 12-24 hours after intravenous injection of the 64Cu-25%-CANF-Comb radiotracer. Patients treated with OMT alone will undergo repeat PET/MRI at 12-18 months, or earlier if they develop symptoms. While 12-18 months is the preferred window for repeat PET/MRI, if imaging during this time frame is not achievable, the patient may return anytime throughout the remainder of the study. PET/MRI changes over time will be used to further understand the biology of carotid plaque evolution after treatment with OMT.

At the time of imaging, the investigators will record baseline medications to include any antiplatelet, statin, anti-hypertension, and diabetes medications (OMT), and basic risk factors and demographic information (e.g. diabetic, hypertensive, smoker, hypercholesterolemia), in addition to the patient's age and sex. Vital signs, a blood draw, and urinalysis will be obtained at baseline and at time of imaging (12-24 hrs after injection). A physical examination will be obtained at baseline and at the time of imaging. Telephone follow-up will occur within 48-72 hours (2-3 days) after discharge and then every 3 months (+/- 5 days) until the end of the study to assess for ipsilateral ischemic cerebrovascular event (TIA, stroke) or remote ipsilateral carotid intervention. This outcomes data will be used to answer the primary objective of this project.

• Changes in 64Cu-CANF-Comb PET signal - OMT [Time frame: 12-18 months (preferred); through study completion, up to 4 years.]
• PET signal relative to presence of targeted receptor, NPR-C and histopathological features of plaque vulnerability - CEA surgery as Treatment [Time frame: Immediately after surgery.]