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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
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2007 (English)In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 28, no 1, 55-62 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The purpose of this study was to evaluate the uptake of Tc-NC100668 into blood clots and elucidate the potential for medications commonly used to treat thromboembolism to interfere with the uptake and retention of Tc-NC100668. METHODS: 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: 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 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 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 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.

Place, publisher, year, edition, pages
2007. Vol. 28, no 1, 55-62 p.
Keyword [en]
99mTc-NC100668, Anticoagulants, Biodistribution, Thrombus
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95165DOI: 10.1097/01.mnm.0000243378.34131.01ISI: 000243360400010PubMedID: 17159550OAI: oai:DiVA.org:uu-95165DiVA: diva2:169273
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2012-03-06Bibliographically approved
In thesis
1. Pre-Clinical Evaluation of a Novel Radiotracer for the Diagnosis of DVT and Pulmonary Embolism.
Open this publication in new window or tab >>Pre-Clinical Evaluation of a Novel Radiotracer for the Diagnosis of DVT and Pulmonary Embolism.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are different aspects of a single condition, venous thrombo-embolic disease (VTE), a major cause of morbidity and mortality in the western world. Rapid diagnosis is critical, as timely medical intervention can have a substantial beneficial effect on the mortality rate.

Irrespective of its presentation, VTE is a difficult disease to diagnose. Pathologies unrelated to VTE can give rise to a clinical presentation similar to DVT or PE, resulting in a false positive diagnosis. This raises the risk of a patient being treated inappropriately. Therefore, there is a need for an agent that has high specificity and sensitivity for the detection of active blood clots, which are amenable to treatment by anticoagulant and/or thrombolytic therapy.

This work describes the pre-clinical efficacy studies performed on one such agent, 99mTc-NC100668. 99mTc-NC100668 is a substrate for factor XIIIa and as a potential physiological, rather than anatomical, marker of VTE it is hoped it will not give rise to the false negative and positive diagnoses that are inherent in the currently available diagnostic techniques, such as the ventilation perfusion (V/Q) scan, multidetector computer tomography or ultrasound.

It is reported in this work that 99mTc-NC100668 uptake and retention in blood clot was rapid and maintained over at least a 4 hour period in a rat model of DVT. Anticoagulant and thrombolytic therapies commonly used to treat thrombosis did not seriously impair the ability of 99mTc-NC100668 to detect thrombi. No significant tissue retention, which could interfere with the ability to image thrombi in vivo, was observed. Biodistribution and plasma clot uptake studies showed that 99mTc complex of gly-NC100194, the major metabolite of 99mTc-NC100668, would be unlikely to affect adversely the clinical utility of the test substance.

The in vitro uptake of 99mTc-NC100668 into forming plasma clots indicated that retention into human blood clots would be comparable with the observations made in the rat preclinical models.

The uptake of 99mTc-NC100668 in vitro and in vivo was much greater than could be accounted for by physical entrapment into the forming blood clots. The reduced uptake of a biologically inactive analogue of 99mTc-NC100668 both in vitro and in vivo indicated that the blood clot uptake and retention of 99mTc-NC100668 was mediated by factor XIIIa.

In conclusion, 99mTc-NC100668 might be useful in the detection of thrombo embolism.

Place, publisher, year, edition, pages
Uppsala: Institutionen för onkologi, radiologi och klinisk immunologi, 2006. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 203
Keyword
Radiology, Radiologisk forskning
Identifiers
urn:nbn:se:uu:diva-7321 (URN)91-554-6726-1 (ISBN)
Public defence
2006-12-08, Föreläsningssalen, Röntgen, Ing. 70, 1 tr, Akademiska sjukhuset, UPPSALA, 13:15
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Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2011-05-19Bibliographically approved

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