(99m)Tc-NC100668, a new tracer for imaging venous thromboemboli: pre-clinical biodistribution and incorporation into plasma clots in vivo and in vitro.
OBJECTIVE
(99m)Tc-NC100668 is a new radiotracer being developed to aid the diagnosis of thromboembolism. The structure of NC100668 is similar to a region of human alpha(2)-antiplasmin, which is a substrate for factor XIIIa (FXIIIa). The purpose of this study was to confirm the uptake of (99m)Tc-NC100668 into forming plasma clot and to establish the biodistribution of (99m)Tc-NC100668 in Wistar rats.


METHODS
The in vitro plasma clot uptake of (99m)Tc-NC100668 and other compounds with known affinities to FXIIIa was measured using a plasma clot assay. The biodistribution and blood clot uptake of radioactivity of (99m)Tc-NC100668 in normal Wistar rats and those bearing experimentally induced deep vein thrombi were investigated.


RESULTS
The in vitro uptake of (99m)Tc-NC100668 was greater than that for [(14)C]dansyl cadaverine, a known substrate of FXIIIa in the plasma clot assay. The biodistribution of (99m)Tc-NC100668 in male and female Wistar rats up to 24 h p.i. showed that radioactivity was rapidly excreted, predominantly into the urine, with very little background tissue retention. In vivo the uptake and retention of (99m)Tc-NC100668 into the blood clot was greater than could be accounted for by non-specific accumulation of the radiotracer within the blood clot.


CONCLUSIONS
(99m)Tc-NC100668 was retained by plasma clots in vitro and blood clots in vivo. No significant tissue retention which could interfere with the ability to image thrombi in vivo was observed. This evidence suggests that (99m)Tc-NC100668 might be useful in the detection of thromboembolism.
Edwards
David
D
Research and Development, GE Healthcare Bio-Sciences, The Grove Centre, White Lion Road, Little Chalfont, HP7 9LL, UK. davidedwards@ge.com
Lewis
Joanne
J
Battle
Mark
M
Lear
Rochelle
R
Farrar
Gill
G
Barnett
D Jon
DJ
Godden
Vanessa
V
Oliveira
Alexandra
A
Coombes
Catherine
C
Ahlström
Håkan
H
D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010455:Peptides / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D020246:Venous Thrombosis / Q000097:blood / Q000000981:diagnostic imaging* / Q000378:metabolism*
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