595 Evaluation of [18F]PyKYNE-losartan in rats using pet imaging

S279

Abstracts

bioprosthesis with multidetector computed tomography (MDCT) and correlated these findings with early clinical events. METHODS: MDCT was performed within one week of SAPIEN XT valve implantation. Geometry of the stent frame was assessed for circularity, minimum (Dmin) and maximum (Dmax) external diameter and expansion ratio at three stent levels: ventricular, mid and aortic. Circularity was defined as an eccentricity index (EI) of less than 0.1 (EI ⫽ 1-Dmin/Dmax) and expansion ratio as a percentage of the measured cross sectional stent area divided by the area for a fully expanded valve. Degree of stent annular apposition and grade of aortic regurgitation(AR) were assessed. RESULTS: 43 patients underwent MDCT. Stents were circular in 95.3% of cases (41/43). The mean expansion ratio was 105.6 ⫾ 7.3% with no valves having an ER of less than 90%. The mean external diameter for the 20, 23, 26 and 29mm valves was 20.0 ⫾ 1.0mm, 23.5 ⫾ 1.0mm, 25.9 ⫾ 0.8mm and 29.0 ⫾ 1.0mm respectively. There was no difference in circularity or expansion ratio from the ventricular to aortic aspect of the stents (EI: 0.02 vs 0.02, P ⫽ 0.78, ER: 104.8% vs 106.5%, P ⫽ 0.28). There was no difference in expansion or circularity in patients with moderate to severe valvular AR compared to trace/mild AR (ER: 108.4% vs 105.3%, P ⫽ 0.37, EI: 0.05 vs 0.02, P ⫽ 0.40). Annular malapposition (12/43, 27.9%) on MDCT was associated with moderate to severe AR in 25%(3/ 12) compared with 6.5% (2/31) with circumferential annular apposition (P ⫽ 0.24). CONCLUSION: The early structural integrity of the SAPIEN XT valve is excellent as demonstrated by full expansion and circularity across all stent levels. Malapposition on MDCT may be associated with paravalvular aortic regurgitation.

595 EVALUATION OF [18F]PYKYNE-LOSARTAN IN RATS USING PET IMAGING NC Arksey, SL Thorn, K Mackasey, RA deKemp, RS Beanlands, JN DaSilva

then eluted into the second reactor vessel for conjugation with azide-modified losartan via ‘click chemistry’. PET Imaging: [18F]FPyKYNE-losartan was injected intravenously into Sprague-Dawley rats (0.5 mCi in 0.5 ml). Dynamic PET imaging was acquired for 60 min in a small animal microPET (Siemens Inveon camera). Regions of interest (ROI) were drawn on the left atrium (blood pool), liver, left kidney and background region. Prior to scan, a 10 min transmission scan was performed for photon attenuation correction. 18 RESULTS: [ F]FPyKYNE-losartan was synthesized in 5-10% yield (specific activity of ⬃500 mCi/␮mol) with high chemical (⬎ 95%) and radiochemical purities (⬎ 97%) using the TRACERLab® FX N Pro (by GE Healthcare) automated dual reactor module. MicroPET images obtained following administration of [18F]FPyKYNE-losartan displayed highest uptake in the liver, followed by the kidneys, where uptake peaked at 2 min with complete washout by 40 min. Good kidney to surrounding tissue contrast was observed (left kidney/blood pool ratio of 12.3 at 12.5 min). Further control scans and blocking studies are currently in process to assess renal binding specificity for AT1R versus AT2R, and in the heart at higher specific activity. 18 CONCLUSION: Pure [ F]FPyKYNE-losartan was synthesized in high yields. This novel tracer, designed from clinically used losartan, shows high potential for monitoring progression of and guiding therapy for various cardiovascular diseases through imaging AT1 receptors. Unlike previous AT1R PET tracers labeled with C-11, which has a 20 min half-life, F-18 has a 110 min half-life allowing for multiple patient scans and for tracer distribution to other imaging facilities. Ontario Preclinical Imaging Consortium (OPIC) grant, Ontario Research Foundation, Ontario Heart and Stroke Foundation (HSF)

Canadian Society of Cardiac Surgeons (CSCS) CSCS016 Poster SURGERY II Tuesday, October 25, 2011

Ottawa, Ontario BACKGROUND: Several cardiac diseases, including hypertrophy,

cardiomyopathy, and myocardial infarction, result in the upregulation of cardiac angiotensin II type 1 receptors (AT1). The ability to detect and quantify this upregulation is important for disease management and prevention. The aim of this study was to evaluate a novel F-18 labeled analog of losartan in rats as a PET tracer for imaging AT1 receptors. It has been previously shown that addition of large substituents at the hydroxyl position of losartan minimally affects its affinity for the AT1R. We synthesized [18F]FPyKYNE-losartan by linking [18F]fluoro-3pent-4-yn-1-yloxypyridine ([18F]FPyKYNE) to azide-modified losartan via ‘click chemistry’. 18 METHODS: Radiochemistry: [ F]FPyKYNE-losartan was synthesized using the fully automated dual reactor module TRACERLab® FX N Pro (by GE Healthcare). Prosthetic group [18F]FPyKYNE was generated in the first reactor vessel

601 THE VALUE OF RISK ALGORITHMS IN PREDICTING OUTCOMES FOR OCTOGENARIANS UNDERGOING AORTIC VALVE REPLACEMENT WITH OR WITHOUT CABG E Elmistekawy, D Tran, J Dupuis, B McDonald, M Ruel, TG Mesana, B Lam Ottawa, Ontario BACKGROUND: Aortic valve replacement (AVR) and AVR with coronary bypass surgery (AVR/CABG) are increasingly performed in octogenarians. Assessment of risk based on predictive algorithms could preclude some octogenarians from the benefits of conventional therapy. The objective of this study was to determine the predictive value of risk algorithms on early and late outcomes in this select group of patients. METHODS: Between 1999 and 2009, 394 octogenarians under-