title: Technetium-99m-nitroimidazole (BMS181321): a positive imaging agent for detecting myocardial ischemia.
abstract: A new technetium-99m-labeled nitroimidazole (BMS181321) has been proposed for positive imaging of myocardial ischemia.
  
  
  METHODS
  An in vivo open-chest canine model of partial coronary occlusion and pacing-induced demand ischemia was used to correlate myocardial retention of BMS181321, following an intravenous injection at peak stress, with regional microsphere blood flow. Postmortem measurements of myocardial BMS181321 activity and flow were correlated with in vivo planar and ex vivo SPECT images. Myocardial and hepatic clearance of BMS181321 was derived from ROI analysis of serial planar images.
  
  
  RESULTS
  Anaerobic metabolism was documented in the ischemic region by selective venous and arterial sampling for lactate and oxygen consumption. Normalized myocardial BMS181321 activity (165% +/- 42% nonischemic) in the central ischemic region (flow < 0.3 ml/min/gm) was significantly greater than activity in normal regions (p < 0.05). Quantitative circumferential analysis of SPECT images revealed a comparable increase in myocardial BMS181321 activity in the ischemic region. Sixty minutes after injection of BMS181321, liver activity was 423% of ischemic myocardial activity.
  
  
  CONCLUSIONS
  BMS181321 was preferentially retained in ischemic but viable canine myocardium and was inversely related to regional myocardial blood flow. Although enhanced retention of BMS181321 was detectable by ex vivo SPECT imaging, an unfavorable heart-to-liver ratio was observed with in vivo planar imaging which may limit its use in clinical myocardial imaging.
authors.affiliation: Department of Internal Medicine, Yale University, School of Medicine, New Haven, Connecticutt 06510, USA.
authors.forename: C Q
authors.initials: CQ
authors.lastname: Shi
authors.forename: A J
authors.initials: AJ
authors.lastname: Sinusas
authors.forename: D P
authors.initials: DP
authors.lastname: Dione
authors.forename: M J
authors.initials: MJ
authors.lastname: Singer
authors.forename: L H
authors.initials: LH
authors.lastname: Young
authors.forename: E N
authors.initials: EN
authors.lastname: Heller
authors.forename: B D
authors.initials: BD
authors.lastname: Rinker
authors.forename: F J
authors.initials: FJ
authors.lastname: Wackers
authors.forename: B L
authors.initials: BL
authors.lastname: Zaret
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D006321:Heart / Q000000981:diagnostic imaging; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D010101:Oxygen Consumption; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007773:Lactates; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; C082027:BMS 181321; D019344:Lactic Acid