Kinetic analysis of technetium-99m-labeled nitroimidazole (BMS-181321) as a tracer of myocardial hypoxia.
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.


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.
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C K
CK
Yale University-VA Positron Emission Tomography Center, West Haven, CT 06516, USA.
Sinusas
A J
AJ
Zaret
B L
BL
Soufer
R
R
D000818:Animals; D015687:Cell Hypoxia; D006321:Heart / Q000000981:diagnostic imaging*; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010101:Oxygen Consumption / Q000502:physiology; D010477:Perfusion; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D013670:Sodium Pertechnetate Tc 99m / Q000493:pharmacokinetics; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics; D013997:Time Factors
D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; C082027:BMS 181321; D013670:Sodium Pertechnetate Tc 99m; D016284:Technetium Tc 99m Pentetate