TY - JOUR T1 - <strong>Evaluation of <sup>18</sup>F-FGA PET/CT for specific imaging of necrotic tissue in a mouse model of coronary artery ligation</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 228 LP - 228 VL - 61 IS - supplement 1 AU - Hariprasad Gali AU - Alexander Mdzinarishvili AU - Andria Hedrick AU - Huining Da AU - Vibhudutta Awasthi Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/228.abstract N2 - 228Objectives: Myocardial infarction (MI) affects 735,000 Americans/year and is a leading cause of death worldwide. Its diagnosis is challenging, especially in presence of atypical symptoms, absence of chest pain, and normal ECG or cardiac troponin profile. Imaging methods also do not accurately discriminate between ischemic and necrotic regions in affected tissue. We posit that information about location and extent of infarct will improve MI diagnosis. We investigated 2-Deoxy-2-[18F]fluoroglucaric acid (FGA), the first radiopharmaceutical for PET imaging of necrosis, in a mouse model of MI. Methods: FGA was synthesized from [18F]fluoro-2-deoxy-2-D-glucose (FDG) by a kit based procedure using TEMPO as a catalyst. MI was produced in CD-1 mice by ligation of left descending coronary artery. PET/CT images were acquired at 1 h, 6 h, 1 d, 3 d, and 4 d after occlusion; FGA (approximately 300 µCi in 300 μl) was injected via the tail vein and the images were acquired 1 h after injection. Standardized uptake values (SUVs) in heart were calculated. Separately, 1 h tissue biodistribution of FGA was assessed in both healthy control and MI mice. Myocardial injury was verified at necropsy by tissue staining with tetrazolium chloride and plasma cardiac troponin levels. For mechanistic analyses of FGA accumulation in necrosis, H9C2 cells were necrosed by H2O2 treatment (50 µM) and exposed to biotin-labeled FGA. Nuclear, mitochondrial, and cytoplasmic fractions were separated by SDS-PAGE for probing with streptavidin-HRP. Results: Kit-based reaction converted FDG quantitatively into FGA within 7 min (radiochemical purity greater than 99%). Uptake of FGA in heart was significantly higher in MI mice than in control mice; images clearly demonstrated FGA accumulation in MI heart. Heart/skeletal muscle ratio was 2.8 in MI mice versus 1.5 in control mice. SUVs from MI mice were significantly higher than those from naïve/sham groups at all time-points of imaging post-MI. In H9C2 cells, we found enhanced uptake of biotin-FGA in nuclear fraction of H2O2-treated cells; cytoplasmic and mitochondrial fractions showed no difference. Conclusions: Results indicate that FGA accumulates in necrotic tissue of MI heart, which could be employed for discriminatory imaging of salvageable ischemic tissue from non-viable tissue. This highly specific and positive predictive value information has potential to impact clinical decisions in management of MI patients. Mechanistically, FGA appears to target hitherto unknown nuclear proteins exposed after necrotic cell death. ER -