title: Evaluation of (99)  (m)TcN-MPO as a new myocardial perfusion imaging agent in normal dogs and in an acute myocardial infarction canine model: comparison with (99)  (m)Tc-sestamibi.
abstract: OBJECTIVE
  (99)  (m)TcN-MPO ([(99)  (m)TcN(mpo)(PNP5)](+): mpo = 2-mercaptopyridine oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic (99)  (m)Tc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi in normal dogs, and to evaluate the potential of (99)  (m)TcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction.
  
  
  METHODS
  Five normal mongrel dogs were injected intravenously with (99)  (m)TcN-MPO. Venous blood samples were collected via a femoral vein catheter at 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 60, and 90 min post-injection (p.i.). Anterior-posterior planar images were acquired by γ-camera at 10, 20, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around the heart, liver, and lungs. The heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in the liver and lung ROI, respectively. For comparison, (99)  (m)Tc-sestamibi was also evaluated in the same five dogs. The interval period between the two examinations was 1 week to eliminate possible interference between these two radiotracers. In addition, single positron emission computed tomography (SPECT) images in the canine infarct model were collected 24 h after myocardial infarction at 30 and 60 min after the administration of (99)  (m)TcN-MPO (n = 4) or (99)  (m)Tc-Sestamibi (n = 4).
  
  
  RESULTS
  It was found that (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi displayed very similar blood clearance characteristics during the first 90 min p.i. Both (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min and less than 5% at 30 min p.i. (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi both showed good heart/lung contrast. The heart/liver ratio of (99)  (m)TcN-MPO increased with time (0.53 ± 0.06 at 10 min, 0.90 ± 0.062 at 30 min, and 1.22 ± 0.06 at 60 min p.i.), whereas the heart/liver ratio of (99)  (m)Tc-Sestamibi remained low at all time points (0.50 ± 0.03 at 10 min, 0.64 ± 0.03 at 30 min, and 0.60 ± 0.02 at 60 min p.i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of (99)  (m)TcN-MPO but not after (99)  (m)Tc-Sestamibi.
  
  
  CONCLUSIONS
  The combination of reasonable heart uptake with rapid hepatobiliary excretion makes (99)  (m)TcN-MPO a promising new radiotracer for myocardial perfusion imaging.
authors.affiliation: Department of Pharmacology, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, Heilongjiang 150001, People's Republic of China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Bu
authors.forename: Renfei
authors.initials: R
authors.lastname: Li
authors.forename: Zhongnan
authors.initials: Z
authors.lastname: Jin
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wen
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.forename: Baozhong
authors.initials: B
authors.lastname: Shen
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D009203:Myocardial Infarction / Q000000981:diagnostic imaging*; D009206:Myocardium / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015609:Organotechnetium Compounds
references.citation: Tohoku J Exp Med. 1995 Nov;177(3):233-48
references.pmid: 8966719
references.citation: J Nucl Med. 2001 Feb;42(2):282-4
references.pmid: 11216527
references.citation: J Nucl Med. 2000 Aug;41(8):1315-7
references.pmid: 10945520
references.citation: Dalton Trans. 2007 Mar 28;(12):1183-93
references.pmid: 17353949
references.citation: Semin Nucl Med. 2001 Oct;31(4):260-77
references.pmid: 11710769
references.citation: Circulation. 2000 Mar 28;101(12):1465-78
references.pmid: 10736294
references.citation: Clin Cancer Res. 2005 Mar 15;11(6):2320-6
references.pmid: 15788683
references.citation: J Med Chem. 1996 Mar 15;39(6):1253-61
references.pmid: 8632432
references.citation: J Cell Biol. 1995 Oct;131(1):137-50
references.pmid: 7559771
references.citation: J Pharmacol Toxicol Methods. 2006 May-Jun;53(3):256-63
references.pmid: 16460969
references.citation: J Nucl Med. 1993 Sep;34(9):1485-93
references.pmid: 8355068
references.citation: Nucl Med Commun. 2008 Sep;29(9):775-81
references.pmid: 18677204
references.citation: J Nucl Cardiol. 2009 Jul-Aug;16(4):571-9
references.pmid: 19288164
references.citation: Semin Nucl Med. 1999 Jul;29(3):221-36
references.pmid: 10433338
references.citation: J Nucl Med. 2004 Dec;45(12):2095-101
references.pmid: 15585487
references.citation: J Nucl Cardiol. 2008 Jul-Aug;15(4):535-46
references.pmid: 18674722
references.citation: Adv Pharmacol. 1993;24:77-97
references.pmid: 8099292
references.citation: J Nucl Med. 2008 Aug;49(8):1299-304
references.pmid: 18632816
references.citation: J Nucl Cardiol. 2001 Jul-Aug;8(4):482-98
references.pmid: 11481571
references.citation: Clin Cancer Res. 2003 Feb;9(2):650-6
references.pmid: 12576431
references.citation: J Nucl Cardiol. 2006 Nov;13(6):779-90
references.pmid: 17174809
references.citation: Bioconjug Chem. 2006 Mar-Apr;17(2):473-84
references.pmid: 16536480
references.citation: J Nucl Cardiol. 2000 Nov-Dec;7(6):701-7
references.pmid: 11144485
references.citation: Nucl Med Biol. 2006 Apr;33(3):419-32
references.pmid: 16631092
references.citation: Semin Nucl Med. 1999 Oct;29(4):280-97
references.pmid: 10534232
references.citation: Nucl Med Biol. 2006 Nov;33(8):1045-53
references.pmid: 17127179
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):213-8
references.pmid: 1448183
references.citation: Nucl Med Biol. 1999 Jul;26(5):563-71
references.pmid: 10473196
references.citation: Nucl Med Commun. 2002 Jul;23(7):689-93
references.pmid: 12089492
references.citation: Bioconjug Chem. 2007 May-Jun;18(3):929-36
references.pmid: 17352455
references.citation: J Cell Physiol. 1993 Nov;157(2):392-402
references.pmid: 7901227