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 Knight, L. C. Articles by Alvarez, V. L. Search for Related Content PubMed PubMed Citation Articles by Knight, L. C. Articles by Alvarez, V. L.

Thrombus Imaging with Technetium-99m Synthetic Peptides Based upon the Binding Domain of a Monoclonal Antibody to Activated Platelets

Nuclear Medicine Department, Temple University School of Medicine, Philadelphia, Pennsylvania
Cytogen Corporation, Princeton, New Jersey

Correspondence: For correspondence or reprints contact: Linda C. Knight, PhD, Nuclear Medicine Dept., Temple University Hospital, 3401 N. Broad St., Philadelphia, PA 19140.

ABSTRACT

Monoclonal antibodies which recognize fibrin or platelets have enabled imaging of vascular thrombi, however, early imaging has been difficult because of the slow blood disappearance of even small antibody fragments. It was theorized that it might be possible to synthesize peptides which possess the same thrombus affinity as monoclonal antibodies, but which would leave the blood pool much more rapidly. Methods: In this study, peptides were synthesized with amino acid sequences based on the primary binding region of the platelet glycoprotein IIb/IIIa-directed monoclonal antibody PAC1. Both termini of the peptides were blocked to prevent rapid proteolysis and a metallothionein-derived sequence was incorporated as a chelating agent for reduced technetium. Results: Technetium-99m-isbaled peptides produced images of fresh clots in the jugular veins of rabbits and day-old thrombi in the femoral veins of dogs within 2 hr after injection. In control experiments, a ^99mTc-labeled nonspecific peptide failed to produce focal images of thrombus. Another control compound, ^99mTc-glucoheptonate, did produce images of fresh clots in rabbits but failed to produce focal images of day-old thrombi. As was hoped, blood clearance of the ^99mTc peptides was rapid, with excretion through the kidneys, however, none of the peptides studied had better thrombus-to-blood ratios than iodinated fibrinogen and all had significantly lower deposition in the thrombus. Conclusion: Using labeled synthetic peptides appears to be technically feasible but the absolute binding to thrombus is not yet sufficient for reliable imaging of pre-existing thrombi.

Key Words: thrombus imaging • ^99mTc peptides • platelet binding

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]

				V. H. D. Bruyn, S. R. Bergmann, B. A. Keyt, and B. E. Sobel Visualization of Thrombi in Pulmonary Arteries With Radiolabeled, Enzymatically Inactivated Tissue-Type Plasminogen Activator Circulation, September 1, 1995; 92(5): 1320 - 1325. [Abstract] [Full Text]