Detection Of Apoptosis With Tc-99m Rh Annexin-V 128 Imaging In Asymptomatic Patients With Carotid Atherosclerotic Plaque

301 Background: Apoptosis plays an important role in the late progression of atherosclerosclerotic plaque and may be useful for identifying advanced and complicated lesions. Objectives: To assess the safety and feasibility of imaging apoptosis in carotid plaques of asymptomatic patients with significant carotid artery disease using 99mTc-rhAnnexin V-128 and compare the uptake to that of normal controls. Methods: In this single centre, single dose, proof of concept, Phase II study, patients were recruited from the carotid ultrasound laboratory. Patients underwent repeat carotid artery ultrasound within 8 weeks of the annexin scan and were categorized as significant carotid artery disease (≥ 50% stenosis in one or both carotid arteries) or normal with no significant carotid artery disease. Patients with previous carotid artery stenting or endarterectomy, stroke or transient ischemic attacks were excluded. Patients underwent planar and SPECT imaging (GE Hawkeye SPECT/CT) at 1 and 2 hours after intravenous injection of ~ 350 MBq of 99mTc-rhAnnexin V-128. Blood samples for hematology and biochemistry and urine samples for urinalysis were collected at baseline for screening and 30 ± 3 days following administration of radiotracer and following any adverse events. Images were reviewed by 3 expert reviewers for identification of focal uptake in the carotid arteries and in the aorta. Quantitative analysis of the planar images was carried out by placing regions of interest in the carotid areas and subclavian region representing venous and arterial activity (target to background (TBR)). Results: Of 582 patients screened, 21 were recruited and 17 completed the protocol (5 normal controls and 12 patients with significant carotid artery disease). There have been 2 adverse events and 1 serious adverse event and none were related to the investigational product. There were no significant changes in any of the blood tests or urinalysis. On visual analysis, only 1 patient of 12 (8%) had significant focal uptake which was present in both carotids and in the arch of the aorta at 1 and 2 hours on both planar and SPECT images. No focal uptake was seen in the carotid arteries or in the aorta of the other 11 patients or in the 5 controls (0/5, 0%). Carotid uptake of annexin (TBR) was significantly greater in the patients with carotid artery disease compared to the controls for both carotid arteries and at 1 and 2 hours (right carotid at 1 hour: 1.18 ± 0.09 vs 1.09 ± 0.03, p=0.012; left carotid at 1 hour: 1.18 ± 0.12 vs 1.05 ± 0.03, p=0.004; right carotid at 2 hours: 1.29 ± 0.13 vs 1.12 ± 0.05, p=0.001; left carotid at 2 hours: 1.32 ± 1.14 vs 1.1 ± 0.05, p=0.0002). Conclusions: 99mTc-rhAnnexin V-128 imaging is safe with no observed adverse events or lab result changes. 99mTc-rhAnnexin V-128 imaging of apoptosis is feasible with excellent image quality at one and 2 hours following tracer injection. Significant focal uptake was identified in 1/12 patients and none of the 5 controls. Quantitative analysis of the planar images showed significantly greater uptake of annexin in patients compared to controls for both carotid arteries and at one and two hours.