title: Myocardial kinetics of Tc-99m glucarate in low flow, hypoxia, and aglycemia.
abstract: BACKGROUND
  Technetium-99m glucarate is a myocardial infarct-avid imaging agent. Recent conflicting and inconclusive reports have suggested that the agent may be taken up by ischemic but viable myocardium. The purposes of this study were (1) to determine conclusively whether there is Tc-99m glucarate uptake in ischemic viable myocardium and (2) to investigate the potential mechanisms for such uptake by studying components of ischemia, namely, low flow, hypoxia, and aglycemia.
  
  
  RESULTS
  Rat hearts were isolated and perfused in a modified Langendorff preparation with a crytalloid perfusate. Tc-99m glucarate was studied in control (n = 6), low-flow (n = 5), hypoxic (n = 5), and aglycemic (n = 5) conditions. The experimental protocol consisted of 20-minute baseline (12 mL/min flow) and 20-minute treatment (low flow at 1 mL/min, hypoxia, or aglycemia), followed by tracer uptake (20 minute) and washout (20 minutes). Activity was monitored with a sodium iodide detector. The tracer was delivered continuously over a 20-minute uptake period. The injected dose was 150 micro Ci (5.6 MBq). Hemodynamics were monitored throughout. Triphenyltetrazolium chloride staining was used to assess myocardial viability. There was no evidence of myocardial necrosis. Low flow tended to delay tracer uptake compared with control for the first 10 minutes, but this did not reach statistical significance. Low flow increased end fractional retention significantly compared with control (mean +/- SEM, 59.0% +/- 0.9% peak vs 41.2% +/- 1.4%, respectively; P <.05). Hypoxia resulted in a trend toward increased uptake; however, this was significant only at one early time point during the uptake phase. Retention in the hypoxia group was similar to control. Tc-99m glucarate uptake was significantly increased in aglycemia from 16 minutes to peak compared with control (1.36% +/- 0.71% injected dose per gram vs 0.91% +/- 0.37% injected dose per gram, respectively; P <.05). Aglycemia produced significantly higher end fractional retention compared with control (51.6% +/- 1.8% peak vs 41.2% +/- 1.4%, respectively; P <.05).
  
  
  CONCLUSIONS
  Tc-99m glucarate myocardial retention is increased in the setting of ischemia, even in the absence of necrosis. This increased retention is not due to hypoxia. Furthermore, the retention is only partially explained by tissue hypoglycemia. Thus low flow per se appears to have a role in this increased retention, probably as a result of delayed flow-dependent washout.
authors.affiliation: University of Tulsa and the William K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Tulsa, Okla.
authors.forename: D R
authors.initials: DR
authors.lastname: Okada
authors.forename: G
authors.initials: G
authors.lastname: Johnson
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: S D
authors.initials: SD
authors.lastname: Hocherman
authors.forename: B A
authors.initials: BA
authors.lastname: Khaw
authors.forename: K Y
authors.initials: KY
authors.lastname: Pak
authors.forename: R D
authors.initials: RD
authors.lastname: Okada
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D003326:Coronary Circulation; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D006321:Heart / Q000000981:diagnostic imaging; D007003:Hypoglycemia / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010865:Pilot Projects; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C067171:technetium Tc 99m glucarate; D005937:Glucaric Acid