Imaging assessment of cardioprotection mediated by a dodecafluoropentane oxygen-carrier administered during myocardial infarction

Abstract

Introduction: The objective of this study was to investigate the cardioprotective effects of a dodecafluoropentane (DDFP)-based perfluorocarbon emulsion (DDFPe) as an artificial carrier for oxygen delivery to ischemic myocardium, using 99mTc-duramycin SPECT imaging. Methods: Rat hearts with Ischemia-reperfusion (I/R) was prepared by coronary ligation for 45-min followed by reperfusion. The feasibility of 99mTc-duramycin in detecting myocardial I/R injury and its kinetic profile were first verified in the ischemic hearts with 2-h reperfusion (n = 6). DDFPe (0.6 mL/kg) was intravenously administered at 10 min after coronary ligation in fifteen rats and saline was given in thirteen rats as controls. 99mTc-duramycin SPECT images were acquired in the DDFPe-treated hearts and saline controls at 2-h (DDFPe-2 h, n = 7 and Saline-2 h, n = 6) or 24-h (DDFPe-24 h, n = 8 and Saline-24 h, n = 7) of reperfusion. Results: SPECT images, showing “hot-spot” 99mTc-duramycin uptake in the ischemic myocardium, exhibited significantly lower radioactive retention and smaller hot-spot size in the DDFPe-2 h and DDFPe-24 h hearts compared to controls. The infarcts in the Saline-24 h hearts extended significantly relative to measurements in the Saline-2 h. The extension of infarct size did not reach a statistical difference between the DDFPe-2 h and DDFPe-24 h hearts. Ex vivo measurement of 99mTc-duramycin activity (%ID/g) was lower in the ischemic area of DDFPe-2 h and DDFPe-24 h than that of the Saline-2 h and Saline-24 h hearts (P < 0.05). The area of injured myocardium, delineated by the uptake of 99mTc-duramycin, extended more substantially outside the infarct zone in the controls. Conclusions: Significant reduction in myocardial I/R injury, as assessed by 99mTc-duramycin cell death imaging and histopathological analysis, was induced by DDFPe treatment after acute myocardial ischemia. 99mTc-duramycin imaging can reveal myocardial cell death in ischemic hearts and may provide a tool for the non-invasive assessment of cardioprotective interventions.

Therapeutic oxygen delivery by perfluorocarbon-based colloids

“…15) [368]. The product also reduced the extent of infarction in a murine stroke model [369], and of myocardial ischemia-reperfusion injury in acutely infarcted rat hearts [370]. Its administration increased cerebral O 2 tension and lessened post-traumatic brain injury hypoxia in rats [371], and substantially reduced infarct size in a murine model of cardiac ischemia [372].…”

Radionuclide imaging of apoptosis for clinical application

“…Apoptosis was also known to participate in the classical pathological processes of cardiovascular disease. Using radionuclide imaging of apoptosis, abundant preclinical trials have been performed in the assessment of atherosclerotic plaques [57,58], aortic aneurysm (AA) [59], ischemia-reperfusion injury [60], and their therapy effectiveness [61][62][63][64]. Some of them have been conducted in humans and obtained positive results.…”

Imaging Cell Death: Focus on Early Evaluation of Tumor Response to Therapy

“…The externalization of PE to cell surface during apoptosis makes PE an alternative target for apoptosis imaging. ,− Moreover, the greater abundance of PE in plasma membrane relative to PS offers more available binding targets, which potentially improves the imaging performance . Duramycin, a low molecular weight peptide capable of specifically binding to PE ( K d ≈ 5 nM), has been the most promising candidate for PE imaging. , 99m Tc-labeled duramycin ( 99m Tc-duramycin) was initially developed as a PE-specific molecular probe, and was demonstrated to be capable of noninvasively detecting apoptosis in different animal models with cerebral and myocardial ischemic/reperfusion injury, − irradiation/chemotherapy-induced tissue injury, − hyperoxia-induced lung injury, tumor necrosis factor-induced systemic inflammatory response syndrome, atherosclerosis, , and aortic aneurysm …”