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Kinetics of a Putative Hypoxic Tracer, ^99mTc-HL91, in Normoxic, Hypoxic, Ischemic, and Stunned Myocardium

Division of Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Osaka
Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba
Institute for Clinical Research, Osaka National Hospital, Chuo-ku, Osaka, Japan

Correspondence: For correspondence or reprints contact: Tsunehiko Nishimura, MD, PhD, Division of Tracer Kinetics, Osaka University Graduate School of Medicine, D9, 2-2 Yamadaoka, Suita, Osaka, 565-0871 Japan.

ABSTRACT

^99mTc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (HL91) was developed as a putative hypoxic reagent. This study focused on the myocardial kinetics of ^99mTc-HL91 in various oxygen levels and perfusion states. Methods: The time-activity curve of ^99mTc-HL91 was measured in isolated perfused rat heart after the bolus infusion. Results: ^99mTc-HL91 was cleared quickly from normoxic hearts, and retention at 30 min after injection was 0.18 ± 0.02 percentage injected dose per gram of wet weight (mean ± SE; n = 6). When the concentration of oxygen bubbling through the perfusate was reduced from 100% to 50%, 20%, 5%, and 0%, retention of <^99mTc-HL91 increased to 0.47 ± 0.03 (n = 5), 0.48 ± 0.03 (n = 5), 0.71 ± 0.01 (n = 5), and 0.70 ± 0.02 (n = 5), respectively (P < 0.05). Compartment analysis revealed that the trapping mechanism, which was dependent on tissue oxygen concentration, determined the retention rate. Although not retained in stunned myocardium (0.17 ± 0.02, n = 5; P = not significant), ^99mTc-HL91 was significantly retained when injected before ischemia (1.06 ± 0.06, n = 5; P < 0.05). Conclusion: These results indicate that retention of ^99mTc-HL91 correlates well with oxygen level in the perfusate, suggesting that the agent may be a useful marker of the severity of myocardial hypoxia.

Key Words: radioisotopes • hypoxia • ischemia • myocardial stunning

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