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.
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.
Edwards
David
D
Research and Development, GE Healthcare Bio-Sciences, The Grove Centre, White Lion Road, Amersham, UK. davidedwards@ge.com
Lewis
Joanne
J
Battle
Mark
M
Lear
Rochelle
R
Farrar
Gill
G
Jon Barnett
D
D
Godden
Vanessa
V
Oliveira
Alexandra
A
Coombes
Catherine
C
Ahlström
Håkan
H
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*
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