Thrombus imaging with technetium-99m synthetic peptides based upon the binding domain of a monoclonal antibody to activated platelets.
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-labeled 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.


CONCLUSIONS
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.
Knight
L C
LC
Nuclear Medicine Department, Temple University School of Medicine, Philadelphia, PA 19140.
Radcliffe
R
R
Maurer
A H
AH
Rodwell
J D
JD
Alvarez
V L
VL
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D004285:Dogs; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015609:Organotechnetium Compounds; D010455:Peptides / Q000138:chemical synthesis*; D011817:Rabbits; D011877:Radionuclide Imaging; D013400:Sugar Acids; D013927:Thrombosis / Q000000981:diagnostic imaging*
D000911:Antibodies, Monoclonal; D015609:Organotechnetium Compounds; D010455:Peptides; D013400:Sugar Acids; C100014:technetium Tc 99m gluceptate