title: Mechanism for myocardial localization and rapid liver clearance of Tc-99m-N-MPO: a new perfusion radiotracer for heart imaging.
abstract: BACKGROUND
  [Tc-99m-N(mpo)(PNP5)](+) (Tc-99m-N-MPO: Hmpo = 2-mercaptopyridine N-oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a new Tc-99m radiotracer useful for myocardial perfusion imaging. The main objective of this study is to elucidate the mechanism for myocardial localization and fast liver clearance of Tc-99m-N-MPO in comparison with Tc-99m-sestamibi ([Tc-99m-(MIBI)(6)](+): MIBI = 2-methoxy-2-methylpropylisonitrile).
  
  
  RESULTS
  Subcellular distribution of Tc-99m-N-MPO and Tc-99m-sestamibi was examined in the excised Sprague-Dawley (SD) rat myocardium. Biodistribution and planar imaging studies were performed using SD rats in the absence/presence of Cyclosporin-A. Due to negative plasma and mitochondrial potentials, 84.5% +/- 3.2% of Tc-99m-N-MPO was found in the mitochondrial fraction as compared to 88.0% +/- 1.5% of Tc-99m-sestamibi. There was no significant difference in their mitochondrial accumulation. Tc-99m-N-MPO was also able to retain its chemical integrity in rat myocardium. Pre-treatment of SD rats with Cys-A result in significant increase in the kidney and liver uptake of Tc-99m-N-MPO.
  
  
  CONCLUSIONS
  Tc-99m-N-MPO and Tc-99m-sestamibi share almost identical subcellular distribution and localization mechanism. The MDR transport function of hepatocytes and renal cells is responsible for the fast clearance kinetics of Tc-99m-N-MPO from liver and kidneys, respectively. Tc-99m-N-MPO is a very promising myocardial perfusion radiotracer with favorable biodistribution properties and rapid liver clearance.
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Young-Seung
authors.initials: YS
authors.lastname: Kim
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.forename: Shizhen
authors.initials: S
authors.lastname: Zhai
authors.forename: Guihua
authors.initials: G
authors.lastname: Hou
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D022781:Hepatocytes / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000187:drug effects*; D008297:Male; D008956:Models, Chemical; D009206:Myocardium / Q000473:pathology*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C532955:technetium 99m (2-mercaptopyridine N-oxide)(N-ethoxyethyl-N,N-bis(2-(bis(3-methoxypropyl)phosphino)ethyl)amine); D016572:Cyclosporine