Targeted PET/CT and PET/MRI Imaging of Vascular Inflammation

Stroke and abdominal aortic aneurysms (AAAs) are common and highly lethal vascular diseases. Angiogenesis and infiltration of inflammatory cells such as macrophages may cause stroke and AAAs. The purpose of this study is to test PET/CT and PET/MRI imaging to specifically detect those diseases using a new developed agent (18F-FPPRGD2) that can target angiogenesis and macrophages.

20 subjects with either carotid bifurcation stenosis of >50% by ultrasound on at least one side (10 patients) or advanced AAAs (10 patients) and surgical intervention planned will be identified from physicians from the Division of Vascular Surgery at Stanford. Either a PET/CT or a PET/MRI will be performed for each subject: PET/CT scans will be performed in 3D mode using GE Discovery 600 or GE Discovery 690 scanners (GE Healthcare). PET/MRI scans will be performed using the novel PET/MRI system at Stanford, including a sensitive PET time-of-flight (TOF) scanner with an advanced 3T MRI scanner. The study patients will receive an intravenous administration of 10mCi of the prescribed radiotracer (18F-FPPRGD2). PET/CT or PET/MRI images will be obtained starting 45-60 minutes after radiotracer administration. For PET/CT, each image acquisition will begin with a non-contrast CT scan obtained from the vertex through the mid-thighs of the subjects. For PET/MRI, non-contrast images of the carotid or aorta will be performed. PET imaging will follow. Patient's vital signs will be monitored during the procedure and a physician will be available if there is need for immediate medical attention. The PET images will be reconstructed with a standard iterative algorithm using GE software release 5.0. After the planned surgery, we will also assess the histopathological correlation between the disease lesions and PET/CT or PET/MRI imaging characteristics.

Aortic Aneurysm, Abdominal, Carotid Stenosis, Atherosclerosis, Angiogenesis, Inflammation, Macrophages, Positron-Emission Tomography, Computerized tomography, Magnetic Resonance Imaging, (18F)FPP(RGD)2

Subjects (with either carotid atherosclerosis stenosis or AAA) will receive a single intravenous injection of 10mCi of 18F-FPPRGD2 and will undergo positron emission tomography/computed tomography (PET/CT) or PET/MRI (PET/magnetic resonance imaging) imaging 45-60 minutes after injection.

The arterial standardized uptake value (SUV) for carotid plaque or AAA will be calculated as the mean pixel activity within the region of interest (ROI). By averaging the SUV values for each artery slice, we will derived a mean SUV value for the entire artery (arterial SUV). This will be corrected for blood activity by division by the average blood SUV estimated from either the inferior vena cava or jugular vein to produce a blood-corrected artery SUV, known as the arterial tissue-to-background ratio (TBR).

After the planned surgical procedure, the accuracy of 18F-FPPRGD2 PET as percent agreement with pathology (including angiogenesis and inflammation assessment) will be calculated.

Inclusion Criteria: Greater than 18 year-old at the time of radiotracer administration Provides written informed consent Patients diagnosed with either carotid artery stenosis or abdominal aortic aneurysms (AAAs) as identified in Vascular Surgery, in whom a surgical procedure is scheduled Able to remain still for duration of an imaging procedure (about one hour). Exclusion Criteria: Less than 18 year-old at the time of radiotracer administration Unable to provide written informed consent Pregnant women Prior carotid or abdominal surgery History of radiation therapy to the neck and abdomen MRI contraindications (including ferromagnetic objects or devices).

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Kitagawa T, Kosuge H, Chang E, James ML, Yamamoto T, Shen B, Chin FT, Gambhir SS, Dalman RL, McConnell MV. Integrin-targeted molecular imaging of experimental abdominal aortic aneurysms by (18)F-labeled Arg-Gly-Asp positron-emission tomography. Circ Cardiovasc Imaging. 2013 Nov;6(6):950-6. doi: 10.1161/CIRCIMAGING.113.000234. Epub 2013 Aug 30.