TY - JOUR
T1 - Imaging assessment of cardioprotection mediated by a dodecafluoropentane oxygen-carrier administered during myocardial infarction
AU - Liu, Zhonglin
AU - Barber, Christy
AU - Gupta, Akash
AU - Wan, Li
AU - Won, Young Wook
AU - Furenlid, Lars R.
AU - Chen, Qin
AU - Desai, Ankit A.
AU - Zhao, Ming
AU - Bull, David A.
AU - Unger, Evan C.
AU - Martin, Diego R.
N1 - Funding Information:
The authors are grateful to Dr. Harrison Barrett, Director of the Center for Gamma-Ray Imaging at University of Arizona , for making the facilities of the Center available for animal imaging studies. We wish to thank Dr. Gail Stevenson for support in animal care and Dr. Luca Caucci for expertise in SPECT data reconstruction. We thank Dr. Chris Pak at MTTI for providing us with duramycin kits for 99m Tc-labeling. This work was supported by the Translational Imaging Program Project Stimulus (TIPPS) Award of the University of Arizona . Research reported in this publication was also partially supported by grants of the National Institutes of Health (NIH): NIBIB P41EB002035 , NHLBI R01HL136603 , and NHLBI R01HL138242 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Evan Unger is the president and chief executive officer of NuvOx Pharma.
Funding Information:
The authors are grateful to Dr. Harrison Barrett, Director of the Center for Gamma-Ray Imaging at University of Arizona, for making the facilities of the Center available for animal imaging studies. We wish to thank Dr. Gail Stevenson for support in animal care and Dr. Luca Caucci for expertise in SPECT data reconstruction. We thank Dr. Chris Pak at MTTI for providing us with duramycin kits for 99mTc-labeling. This work was supported by the Translational Imaging Program Project Stimulus (TIPPS) Award of the University of Arizona. Research reported in this publication was also partially supported by grants of the National Institutes of Health (NIH): NIBIB P41EB002035, NHLBI R01HL136603, and NHLBI R01HL138242. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Evan Unger is the president and chief executive officer of NuvOx Pharma.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - Cell death imaging
KW - Dodecafluoropentane perfluorocarbon emulsion
KW - Myocardial ischemia-reperfusion
KW - Phosphatidylethanolamine
KW - Tc-Duramycin
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U2 - 10.1016/j.nucmedbio.2019.01.004
DO - 10.1016/j.nucmedbio.2019.01.004
M3 - Article
C2 - 30772168
AN - SCOPUS:85061543873
SN - 0969-8051
VL - 70
SP - 67
EP - 77
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
ER -