Abstract 4369229: Validation of a Novel Reactive Oxygen Species-Targeted SPECT Tracer ⁶⁷ Ga-Galuminox in Pig Model of Myocardial Ischemia-Reperfusion Injury

Abstract

Background: Reactive oxygen species (ROS) plays a major role in the pathogenesis of myocardial ischemia-reperfusion injury (IRI). However, molecular imaging probes enabling the in vivo detection of ROS are limited. Aim: To evaluate and validate the myocardial uptake of a novel 67 Ga-labeled SPECT tracer, 67 Ga-Galuminox, for the in vivo quantitative assessment of myocardial IRI in relation to myocardial perfusion. Methods: Three anesthetized Yorkshire pigs were subjected to myocardial IRI by 90 min balloon occlusion in the left anterior descending artery and reperfusion. In vivo SPECT/CT images of the heart were acquired on the day of injury or 3 days post injury with hybrid 360° CZT SPECT 64-slice CT (Veriton-CT 400, Spectrum Dynamics) with 67 Ga-Galuminox (93 keV) in evaluation of ROS and 99m Tc-Tetrofosmin (140.5 keV) to define myocardial perfusion. Quantitative segmental image analysis was performed and compared with tissue gamma well counting for the corresponding epicardial (EP) and endocardial (EN) segments. Results: Myocardial uptake of 67 Ga-Galuminox was increased in the area at risk as defined by 99m Tc-Tetrofosmin (Figure 1). 67 Ga-Galuminox uptake assessed by in vivo SPECT correlated positively with the tissue well counting in corresponding EP (r=0.57, p<0.005) and EN (r=0.43, p=0.002) segments. Uptake of 67 Ga-Galuminox was significantly higher in the infarcted segments compared to remote area by both in vivo SPECT and gamma well counting. Regional myocardial 99m Tc-Tetrofosmin and 67 Ga-Galuminox uptake were negatively correlated in EP (r=-0.78, p<0.001) and EN (r=-0.8, p<0.001). Conclusions: Myocardial 67 Ga-Galuminox SPECT/CT imaging provides excellent image quality, enabling accurate non-invasive quantification of EN and EP activation of ROS in our porcine model of myocardial IRI.