(Circulation. 1995;92:1261-1268.)
© 1995 American Heart Association, Inc.
Articles |
Kinetic Analysis of Technetium-99m-Labeled Nitroimidazole (BMS-181321) as a Tracer of Myocardial Hypoxia
Presented in part at the American College of Cardiology, Atlanta, Ga, 1994, and at the Society of Nuclear Medicine, Orlando, Fla, 1994.
From the Yale University–VA Positron Emission Tomography Center (C.K.N., R.S.), Department of Veterans Affairs, West Haven, Conn, and the Division of Nuclear Medicine (C.K.N., A.J.S., B.L.Z., R.S.), Department of Diagnostic Radiology, and the Division of Cardiovascular Medicine (A.J.S., B.L.Z., R.S.), Department of Medicine, Yale University School of Medicine, New Haven, Conn.
Correspondence to Chin K. Ng, PhD, Yale University/VA PET Center, VA Medical Center (115A), 950 Campbell Ave, West Haven, CT 06516.
Background Experimental data have indicated that [99mTc]- nitroimidazole (BMS-181321) is preferentially taken up in hypoxic tissue; its kinetics, however, has not been fully investigated. The purpose of this study was to address the relation between perfusate oxygen level and myocardial retention of [99mTc]nitroimidazole.
Methods and Results Bolus injection and constant infusion experiments were performed in Langendorff buffer–perfused rat hearts in normoxic and hypoxic conditions. Data were acquired with a pair of NaI detectors. The initial clearance rate of [99mTc]nitroimidazole was approximately 20 seconds and independent of perfusate oxygen level. The slow clearance rate was greater than 3 hours in all perfusion conditions. The tissue retention of [99mTc]nitroimidazole varied from 0.61±0.14% in normoxic conditions to 5.94±1.16% in the most severe hypoxic conditions. In addition, tissue retention was inversely proportional to perfusate oxygen level in a sigmoidal manner. The constant infusion experiments established that the binding rate at 25% oxygen level (1.94±0.38 mL of perfusate/min-g dry wt) was twofold of that at 40% and sevenfold at 100%. The binding rate of [99mTc]nitroimidazole was independent of the perfusion sequence, suggesting irreversible binding.
Conclusions These data indicate that [99mTc]nitroimidazole may be a useful tracer for the identification of myocardial hypoxia. A sigmoidal relation was demonstrated for the uptake of the tracer, which suggests that a threshold level of hypoxia is necessary for the uptake of the tracer.
Key Words: hypoxia • ischemia
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