title: Kinetics of a putative hypoxic tracer, 99mTc-HL91, in normoxic, hypoxic, ischemic, and stunned myocardium.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Imahashi
authors.forename: K
authors.initials: K
authors.lastname: Morishita
authors.forename: H
authors.initials: H
authors.lastname: Kusuoka
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamichi
authors.forename: S
authors.initials: S
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Shirakami
authors.forename: M
authors.initials: M
authors.lastname: Kato-Azuma
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D006321:Heart / Q000000981:diagnostic imaging*; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging*; D017682:Myocardial Stunning / Q000000981:diagnostic imaging; D009206:Myocardium / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010091:Oximes / Q000493:pharmacokinetics; D010101:Oxygen Consumption; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015609:Organotechnetium Compounds; D010091:Oximes; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime