HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thakur, M. L. Articles by Shi, R. Search for Related Content PubMed PubMed Citation Articles by Thakur, M. L. Articles by Shi, R.

Imaging Vascular Thrombosis with ^99mTc-Labeled Fibrin -Chain Peptide

Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

Correspondence: For correspondence or reprints contact: Mathew L. Thakur, PhD, Thomas Jefferson University Hospital, 1020 Locust St., Ste. 359 JAH, Philadelphia, PA 19107.

ABSTRACT

An agent that permits scintigraphic detection of chronic deep venous thrombosis (DVT) or pulmonary embolism (PE) would be a welcome addition to the armamentarium of nuclear medicine. Because fibrin is the integral part of each clot, old or fresh, we hypothesized that a ^99mTc-labeled fibrin -chain N-terminal peptide, Gly-Pro-Arg-Pro-Pro, that binds to the C-terminal portion of the -chain of fibrin can detect DVT and PE. Methods: The peptide was modified to Gly-Pro-Arg-Pro-Pro-Aba-Gly-Gly-(D)-Ala-Gly to permit efficient binding of ^99mTc (^99mTc-TP 850). The stability of the peptide was examined in vitro as well as in vivo. The ability of the agent to bind to rabbit, dog, and human fibrin and to inhibit adenosine diphosphate-induced platelet aggregation was examined. Blood clearance and 3-h tissue distribution were studied. DVT was induced in 8 rabbits using a stimulating electrode and in 2 rabbits by inserting a thrombin-soaked suture. PE was induced in 6 additional rabbits by introducing tantalum-impregnated blood clots into the right atrium, and the rabbits were radiographed to locate the emboli. ^99mTc-TP 850 was then injected through a lateral ear vein, and each rabbit was imaged for up to 3 h. The rabbits were then killed, the heart and lungs were dissected and radiographed and the clots were harvested so that clot-to-blood radioactivity ratios could be determined. Results: The peptide analog permitted efficient incorporation of ^99mTc, which was stable in vitro and in vivo. The blood clearance was biphasic, with an phase half-life of approximately 4 min (20%)and a ß phase half-life of approximately 13 min (88%). The mean binding of ^99mTc-TP 850 to human, dog, and rabbit fibrin was 46% ± 2%, 60% ± 3%, and 56% ± 2.5%, respectively, and the inhibitory concentration of 50% for dog and rabbit platelet aggregation was 236 µm and 167 µm, respectively. All clots, including 24-h-old pulmonary emboli, were delineated. The radioactivity associated with clots varied from 0.01 to 0.09 %ID/g, with clot-to-blood radioactivity ratios ranging from 1.2 to 12.0. However, 48-h-old pulmonary emboli had lysed and were seen neither by radiography nor by scintigraphy. Conclusion: A fibrin -chain, N-terminal peptide that binds to the C-terminal portion of the -chain of fibrin has been modified and labeled with ^99mTc. The resultant peptide is stable in vitro and in vivo; binds to human, dog, and rabbit fibrin in large quantities; and inhibits platelet aggregation. The peptide clears rapidly from the blood and delineates experimental DVT and PE in rabbits. This agent is worthy of further investigation.

Key Words: ^99mTc-fibrin -chain peptide • imaging deep venous thrombosis and pulmonary embolism • ^99mTc-labeled peptide

This article has been cited by other articles:

				M. R. Aruva, J. Daviau, S. S. Sharma, and M. L. Thakur Imaging Thromboembolism with Fibrin-Avid 99mTc-Peptide: Evaluation in Swine J. Nucl. Med., January 1, 2006; 47(1): 155 - 162. [Abstract] [Full Text] [PDF]

				X. Tian, M. R. Aruva, W. Qin, W. Zhu, K. T. Duffy, E. R. Sauter, M. L. Thakur, and E. Wickstrom External Imaging of CCND1 Cancer Gene Activity in Experimental Human Breast Cancer Xenografts with 99mTc-Peptide-Peptide Nucleic Acid-Peptide Chimeras J. Nucl. Med., December 1, 2004; 45(12): 2070 - 2082. [Abstract] [Full Text] [PDF]