Kinetics of a putative hypoxic tracer, 99mTc-HL91, in normoxic, hypoxic, ischemic, and stunned myocardium

Kenichi Imahashi, Kenichi Morishita, Hideo Kusuoka, Yoshihiro Yamamichi, Shinji Hasegawa, Katsuji Hashimoto, Yoshifumi Shirakami, Makoto Kato-Azuma, Tsunehiko Nishimura

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1102-1107
Number of pages6
JournalJournal of Nuclear Medicine
Volume41
Issue number6
StatePublished - Jun 2000
Externally publishedYes

Fingerprint

Myocardial Stunning
Oxygen
technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime
Ischemia
Perfusion
Weights and Measures
Injections

Keywords

  • Hypoxia
  • Ischemia
  • Myocardial stunning
  • Radioisotopes

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Imahashi, K., Morishita, K., Kusuoka, H., Yamamichi, Y., Hasegawa, S., Hashimoto, K., ... Nishimura, T. (2000). Kinetics of a putative hypoxic tracer, 99mTc-HL91, in normoxic, hypoxic, ischemic, and stunned myocardium. Journal of Nuclear Medicine, 41(6), 1102-1107.

Kinetics of a putative hypoxic tracer, 99mTc-HL91, in normoxic, hypoxic, ischemic, and stunned myocardium. / Imahashi, Kenichi; Morishita, Kenichi; Kusuoka, Hideo; Yamamichi, Yoshihiro; Hasegawa, Shinji; Hashimoto, Katsuji; Shirakami, Yoshifumi; Kato-Azuma, Makoto; Nishimura, Tsunehiko.

In: Journal of Nuclear Medicine, Vol. 41, No. 6, 06.2000, p. 1102-1107.

Research output: Contribution to journalArticle

Imahashi, K, Morishita, K, Kusuoka, H, Yamamichi, Y, Hasegawa, S, Hashimoto, K, Shirakami, Y, Kato-Azuma, M & Nishimura, T 2000, 'Kinetics of a putative hypoxic tracer, 99mTc-HL91, in normoxic, hypoxic, ischemic, and stunned myocardium', Journal of Nuclear Medicine, vol. 41, no. 6, pp. 1102-1107.
Imahashi K, Morishita K, Kusuoka H, Yamamichi Y, Hasegawa S, Hashimoto K et al. Kinetics of a putative hypoxic tracer, 99mTc-HL91, in normoxic, hypoxic, ischemic, and stunned myocardium. Journal of Nuclear Medicine. 2000 Jun;41(6):1102-1107.
Imahashi, Kenichi ; Morishita, Kenichi ; Kusuoka, Hideo ; Yamamichi, Yoshihiro ; Hasegawa, Shinji ; Hashimoto, Katsuji ; Shirakami, Yoshifumi ; Kato-Azuma, Makoto ; Nishimura, Tsunehiko. / Kinetics of a putative hypoxic tracer, 99mTc-HL91, in normoxic, hypoxic, ischemic, and stunned myocardium. In: Journal of Nuclear Medicine. 2000 ; Vol. 41, No. 6. pp. 1102-1107.
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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.",
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AU - Imahashi, Kenichi

AU - Morishita, Kenichi

AU - Kusuoka, Hideo

AU - Yamamichi, Yoshihiro

AU - Hasegawa, Shinji

AU - Hashimoto, Katsuji

AU - Shirakami, Yoshifumi

AU - Kato-Azuma, Makoto

AU - Nishimura, Tsunehiko

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N2 - 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.

AB - 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.

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KW - Ischemia

KW - Myocardial stunning

KW - Radioisotopes

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