title: BMS-747158-02: a novel PET myocardial perfusion imaging agent.
abstract: BACKGROUND
  BMS-747158-02 is a fluorine 18-labeled pyridaben derivative designed as a new myocardial perfusion imaging agent for use with positron emission tomography (PET). This study evaluated BMS-747158-02 in animal models of cardiac perfusion and compared it with established single photon emission computed tomography agents.
  
  
  RESULTS
  In a rat biodistribution study, BMS-747158-02 (15 microCi) had substantially higher myocardial uptake than technetium 99m sestamibi (100 microCi) at 15 minutes (3.5% +/- 0.3% %ID/g vs 1.9% +/- 0.1% %ID/g) and 120 minutes (3.2% +/- 0.4% of injected dose per gram vs 1.8% +/- 0.0% of injected dose per gram) after intravenous administration. Uptake ratios of heart to lung and liver at 60 minutes were also higher for BMS-747158-02 (12.7 +/- 1.4 and 3.7 +/- 0.2, respectively) than Tc-99m sestamibi (5.9 +/- 0.5 and 2.4 +/- 0.4, respectively). In an isolated rabbit heart model at flow rates of 1.66 to 5.06 mL x min(-1).g(-1) wet left ventricular weight, the net BMS-747158-02 heart uptake increased proportionally (0.93 +/- 0.15 to 2.44 +/- 0.40 mL.min(-1) x g(-1)) and to a greater extent than that of thallium 201 (0.76 +/- 0.02 to 1.11 +/- 0.02 mL x min(-1) x g(-1)) or Tc-99m sestamibi (0.49 +/- 0.03 to 0.77 +/- 0.08 mL x min(-1) x g(-1)). PET imaging with BMS-747158-02 showed a clear and sustained cardiac uptake in rats, rabbits, and nonhuman primates with minimal lung interference and rapid liver clearance. Myocardial perfusion deficit zones created by either permanent left coronary ligation or reperfusion after ligation in rats were both clearly identified on PET cardiac images of BMS-747158-02 and had good agreement with in vitro histology.
  
  
  CONCLUSIONS
  BMS-747158-02 exhibited high and sustained cardiac uptake that was proportional to blood flow, and it represents a new class of PET myocardial perfusion imaging agent.
authors.affiliation: Discovery Biology, Bristol-Myers Squibb Medical Imaging, North Billerica, MA, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Mary T
authors.initials: MT
authors.lastname: Guaraldi
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mistry
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kagan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McDonald
authors.forename: Kenneth
authors.initials: K
authors.lastname: Drew
authors.forename: Heike
authors.initials: H
authors.lastname: Radeke
authors.forename: Michael
authors.initials: M
authors.lastname: Azure
authors.forename: Ajay
authors.initials: A
authors.lastname: Purohit
authors.forename: David S
authors.initials: DS
authors.lastname: Casebier
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007089:Image Enhancement / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011724:Pyridazines / Q000493:pharmacokinetics*; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: C525920:BMS 747158-02; D011724:Pyridazines; D019275:Radiopharmaceuticals