Thrombus imaging: a comparison of radiolabeled GC4 and T2G1s fibrin-specific monoclonal antibodies.

Radioimmunoimaging of experimentally-induced canine thrombi has previously been achieved with iodine-131- and indium-111-labeled (131I and 111In) anti-fibrin T2G1s monoclonal antibody (MAb). We now compare T2G1s to another anti-fibrin MAb, designated GC4, for imaging fresh and aged canine thrombi. GC4 is specific for a neoepitope exposed on fibrin later in the thrombolytic process after plasmin digestion. Femoral venous thrombi were induced in six groups of dogs, each containing three dogs. In two groups, the MAbs were compared when the thrombi were 3-hr or 3-days old at the time of injection, and the dogs were killed at 48 hr. In thrombi 3-hr-old, the GC4/T2G1s concentration ratio averaged 0.53 compared to 1.9 in 3-day-old thrombi. Two groups of dogs with thrombi 1- or 3-days-old were heparinized before MAb injection and were killed at 24 hr. The heparinized dogs with thrombi 1- or 3-days-old had GC4/T2G1s mean ratios of 2.3 and 2.9, respectively. In the unheparinized groups, the corresponding ratios were 1.1 and 1.9. GC4 may be more useful for clinical thrombus imaging than T2G1s because spontaneous venous thrombi are usually several days old at the time of presentation and patients are often heparinized immediately.

Thrombus imaging with indium-111 and iodine-131-labeled fibrin-specific monoclonal antibody and its F(ab')2 and Fab fragments.

We have previously reported successful imaging of fresh (2-4 hr old) and aged (1-5 days old) canine thrombi with 131I-labeled intact monoclonal antibody (MAb) specific for fibrin. We now report thrombus imaging with 131I-labeled F(ab')2 and Fab and 111In-labeled intact MAb, F(ab')2, and Fab. Indium-111-labeled F(ab')2 proved to be the best imaging agent due to less nonspecific binding in the liver than whole IgG. Image quality was improved by the higher administered dose permissible with 111In and its better physical characteristics for imaging, compared to 131I. Immunofluorescence of fresh human histologic sections showed intact MAb and F(ab')2 binding to thrombi, pulmonary emboli, and atherosclerotic plaques, strengthening the feasibility of clinical thrombus imaging.

Radioimmunoimaging of venous thrombi using iodine-131 monoclonal antibody.

Murine monoclonal antibody (Mab) specific for the NH2-terminal region of human fibrin, but not cross-reactive with fibrinogen, was used in radioimmuno-imaging of fresh, induced venous thrombi in three dogs. Iodine-131-labeled Mab was injected intravenously, with iodine 125-labeled polyclonal murine gamma-G globulin (IgG) simultaneously injected as a control. Images were strongly positive at 24 and 48 hours in all three animals, with thrombus-to-blood and thrombus-to-muscle ratios of 8.4 and 228.0, respectively, for I-131-labeled Mab; these ratios for control IgG were 1.2 and 13.0. Radioimmunodetection of thrombi in vivo is feasible in dogs and may have clinical application since Mab is specific to human fibrin.

Imaging fresh venous thrombi in the dog with I-131 and In-111 labeled fibrin-specific monoclonal antibody and F(ab')2 fragments.

The authors report success in imaging thrombi using labeled monoclonal antibody or antibody fragments. An In-111 labeled antibody fragment appears to be the best imaging agent studied to date.

Aged venous thrombi: radioimmunoimaging with fibrin-specific monoclonal antibody.

Radioimmunoimaging of fresh canine venous thrombi with a murine monoclonal antibody specific for human and dog fibrin has been reported. Successful imaging of canine deep venous thrombi 1, 3, and 5 days old at the time of antibody injection is reported. Images were positive in all dogs, and the uptake of fibrin-specific antibody was equivalent to that of fresh thrombi.