TY - JOUR
T1 - Technetium 99m-HL-91
T2 - A potential new marker of myocardial viability assessed by nuclear imaging early after reperfusion
AU - Johnson, Gerald
AU - Nguyen, Kiem N.
AU - Liu, Zhonglin
AU - Okada, Robert D.
N1 - Funding Information:
Objective. 99mTcIHL-91 (Prognox) is a potential new hypoxia-avid myocardial imaging agent. The purpose of this study was to determine whether this tracer would demonstrate increased activity in nonviable myocardium in vivo. Methods and Results. A 3-hour left circumflex artery (LCx) occlusion was followed by 1 hour of reperfusion, injection of 99mTcIHL-91 (185 MBq), and 2 hours of gamma camera imaging in 6 open-chest canine experiments. Microspheres were injected during baseline, at occlusion, at the time of tracer injection, and at the end of the experiment. After the animals were killed, heart slices were imaged. Blood flow and tracer activity were determined by well counting. Mean infarct size was 19.2% _+ 2.2% (SEM). All six dogs demonstrated no increased 99mTc-HL-91 myocardial activity other than small foci on in vivo and ex vivo gamma camera images. The mean large region of interest (ROI)-determined LCx/LAD (left anterior descending) ratio was 1.10 _+ 0.03 in vivo, and 1.0 _+ 0.02 ex vivo. Mean clearance curves from LCx and LAD ROI were not significantly different, and 2-hour retention was 15.2% _+ 2.1% for the LCx and 18.6% _+ 2.7% for the LAD (p = NS). ROI clearance curves demonstrated biexponential clearance over the first hour and linear clearance over the second hour. Myocardial blood flow (microspheres) versus well-counted tracer uptake curves were linear with near-zero slopes for viable tissue, nonviable tissue, and mosaic tissue. Blood clearance was triexponential with a 2-hour retention of 7.8% _+ 1.1%. Conclusions. In contrast to viable ischemic tissue, normal and nonviable myocardium demonstrate similar 99mTc-HL-91 uptake and retention kinetics. This agent warrants further clinical studies in situations where there is a need to differentiate ischemic viable from nonviable myocardium. (J Nucl Cardiol 1998;5:285-94.) Key Words: 99mTc-HL-91 kinetics • myocardial viability • nuclear imaging • infarct • Prognox • hypoxia 99mTc-HL-91 (where HL-91 = 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime) (Prognox) is a new potential "hot spot" hypoxia-avid myocardial imaging agent. 1 Using a perfused isolated heart model, our laboratory reported increased myocardial 99mTc-HL-91 uptake and retention in models of low-flow ischemia and normal-flow hypoxia. 2 Subsequent canine studies clearly demonstrated selective increased myocardial 99mTc-HL-91 uptake and retention in an ischemic zone relative to a nonischemic zone in an in vivo model using gamma cam- From the William K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Tulsa, Oklahoma. Received for publicationOct. 6, 1997; revision accepted Feb. 2, 1998. Supported in part by NycomedA mersham p/c, Buckinghamshire, UK. Reprint requests: Gerald Johnson III, PhD, William K. Warren Medical Research Institute, 6465 SouthY ale, Suite 1010, Tulsa, OK 74136; gerald-johnson @u okhsc, edu. Copyright © 1998 by American Society of Nuclear Cardiology. 1071-3581/98/$5.00 + 0 4311189264 era imaging) However, both of these studies investigated ischemic but viable myocardium. To determine whether 99mTc-HL-91 could also be used as a marker of viability, we performed studies with a perfused isolated heart model of myocardial cell death using both cyanide and ischemia/reperfusion injury. 4 These studies demonstrated no increased tracer retention in nonviable tissue. However, these studies were undertaken in a global model of injury and without imaging. Thus the current study was performed to determine the pattern of uptake of 99mTc-HL-91 in nonviable myocardial tissue subjected to severe ischemia/reperfusion injury in an in vivo canine model using gamma camera imaging.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - Objective. 99mTc-HL-91 (Prognox) is a potential new hypoxia-avid myocardial imaging agent. The purpose of this study was to determine whether this tracer would demonstrate increased activity in nonviable myocardium in vivo. Methods and Results. A 3-hour left circumflex artery (LCx) occlusion was followed by 1 hour of reperfusion, injection of 99mTc-HL-91 (185 MBq), and 2 hours of gamma camera imaging in 6 open-chest canine experiments. Microspheres were injected during baseline, at occlusion, at the time of tracer injection, and at the end of the experiment. After the animals were killed, heart slices were imaged. Blood flow and tracer activity were determined by well counting. Mean infarct size was 19.2% ± 2.2% (SEM). All six dogs demonstrated no increased 99mTc-HL-91 myocardial activity other than small foci on in vivo and ex vivo gamma camera images. The mean large region of interest (ROI)-determined LCx/LAD (left anterior descending) ratio was 1.10 ± 0.03 in vivo, and 1.0 ± 0.02 ex vivo. Mean clearance curves from LCx and LAD ROI were not significantly different, and 2-hour retention was 15.2% ± 2.1% for the LCx and 18.6% ± 2.7% for the LAD (p = NS). ROI clearance curves demonstrated biexponential clearance over the first hour and linear clearance over the second hour. Myocardial blood flow (microspheres) versus well-counted tracer uptake curves were linear with near-zero slopes for viable tissue, nonviable tissue, and mosaic tissue. Blood clearance was triexponential with a 2-hour retention of 7.8% ± 1.1%. Conclusions. In contrast to viable ischemic tissue, normal and nonviable myocardium demonstrate similar 99mTc-HL-91 uptake and retention kinetics. This agent warrants further clinical studies in situations where there is a need to differentiate ischemic viable from nonviable myocardium.
AB - Objective. 99mTc-HL-91 (Prognox) is a potential new hypoxia-avid myocardial imaging agent. The purpose of this study was to determine whether this tracer would demonstrate increased activity in nonviable myocardium in vivo. Methods and Results. A 3-hour left circumflex artery (LCx) occlusion was followed by 1 hour of reperfusion, injection of 99mTc-HL-91 (185 MBq), and 2 hours of gamma camera imaging in 6 open-chest canine experiments. Microspheres were injected during baseline, at occlusion, at the time of tracer injection, and at the end of the experiment. After the animals were killed, heart slices were imaged. Blood flow and tracer activity were determined by well counting. Mean infarct size was 19.2% ± 2.2% (SEM). All six dogs demonstrated no increased 99mTc-HL-91 myocardial activity other than small foci on in vivo and ex vivo gamma camera images. The mean large region of interest (ROI)-determined LCx/LAD (left anterior descending) ratio was 1.10 ± 0.03 in vivo, and 1.0 ± 0.02 ex vivo. Mean clearance curves from LCx and LAD ROI were not significantly different, and 2-hour retention was 15.2% ± 2.1% for the LCx and 18.6% ± 2.7% for the LAD (p = NS). ROI clearance curves demonstrated biexponential clearance over the first hour and linear clearance over the second hour. Myocardial blood flow (microspheres) versus well-counted tracer uptake curves were linear with near-zero slopes for viable tissue, nonviable tissue, and mosaic tissue. Blood clearance was triexponential with a 2-hour retention of 7.8% ± 1.1%. Conclusions. In contrast to viable ischemic tissue, normal and nonviable myocardium demonstrate similar 99mTc-HL-91 uptake and retention kinetics. This agent warrants further clinical studies in situations where there is a need to differentiate ischemic viable from nonviable myocardium.
KW - 99mTc-HL-91 kinetics
KW - Hypoxia
KW - Infarct
KW - Myocardial viability
KW - Nuclear imaging
KW - Prognox
UR - http://www.scopus.com/inward/record.url?scp=13144261782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13144261782&partnerID=8YFLogxK
U2 - 10.1016/S1071-3581(98)90130-1
DO - 10.1016/S1071-3581(98)90130-1
M3 - Article
C2 - 9669583
AN - SCOPUS:13144261782
VL - 5
SP - 285
EP - 294
JO - Journal of Nuclear Cardiology
JF - Journal of Nuclear Cardiology
SN - 1071-3581
IS - 3
ER -