title: 99mTc-NC100668, an agent for imaging venous thromboembolism: The effect of anticoagulant or thrombolytic therapy on the uptake and retention of radioactivity in blood clots in vivo.
abstract: BACKGROUND
  The purpose of this study was to evaluate the uptake of (99m)Tc-NC100668 into blood clots and elucidate the potential for medications commonly used to treat thromboembolism to interfere with the uptake and retention of (99m)Tc-NC100668.
  
  
  METHODS
  (99m)Tc-NC100668 in vivo uptake and retention in a range of blood clot of various ages (up to 4 h. old) and in the presence of anticoagulants or thrombolytic therapies was measured in a rat model of deep vein thrombosis.
  
  
  RESULTS
  (99m)Tc-NC100668 was rapidly absorbed into and retained by blood clots and was not significantly affected by the presence of unfractionated or low molecular weight heparin or thrombin inhibitor. Tissue plasminogen activator reduced the uptake of (99m)Tc-NC100668 into blood clot by a factor of 3 when adjusted to allow for changes in the weight of the blood clot.
  
  
  CONCLUSIONS
  This study has demonstrated that the uptake and retention of (99m)Tc-NC100668 into blood clots in the rat model of deep vein thrombosis is rapid and maintained over at least a 4 h. post-injection period. It has been shown that (99m)Tc-NC100668 is retained in blood clots even in the presence of therapeutic doses of those anticoagulant and thrombolytic therapies typically used to treat pulmonary embolism and venous thrombosis.
authors.affiliation: Research and Development, GE Healthcare Bio-Sciences, The Grove Centre, White Lion Road, Amersham, UK. davidedwards@ge.com
authors.forename: David
authors.initials: D
authors.lastname: Edwards
authors.forename: Joanne
authors.initials: J
authors.lastname: Lewis
authors.forename: Mark
authors.initials: M
authors.lastname: Battle
authors.forename: Rochelle
authors.initials: R
authors.lastname: Lear
authors.forename: Gill
authors.initials: G
authors.lastname: Farrar
authors.forename: D
authors.initials: D
authors.lastname: Jon Barnett
authors.forename: Vanessa
authors.initials: V
authors.lastname: Godden
authors.forename: Alexandra
authors.initials: A
authors.lastname: Oliveira
authors.forename: Catherine
authors.initials: C
authors.lastname: Coombes
authors.forename: Håkan
authors.initials: H
authors.lastname: Ahlström
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008956:Models, Chemical; D010455:Peptides / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000493:pharmacokinetics*; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D020246:Venous Thrombosis / Q000175:diagnosis* / Q000000981:diagnostic imaging*
chemical_list: D000925:Anticoagulants; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D019275:Radiopharmaceuticals; C507860:acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-Tyr(3-iodo)-Thr-Leu-Leu-Lys-Gly-NC100194; D013667:Technetium; D010959:Tissue Plasminogen Activator