Improved imaging of deep venous thrombi during anticoagulation using radiolabelled anti-D-dimer antibodies.
OBJECTIVE
Radiolabelled anti-fibrin antibodies have not yet enabled reliable and practical diagnosis of venous thromboembolism. However, previous unsuccessful clinical trials were performed with anti-fibrin beta-chain antibodies that do not optimally bind to thrombi during anticoagulation. The current experiments were performed to determine if radiolabelled anti-D-dimer antibodies more reliably allowed nuclear medicine imaging of deep venous thrombi during anticoagulation than anti-beta-chain antibodies.


METHODS
Dogs with pre-existing unilateral femoral vein thrombi were anticoagulated with heparin (300 units.kg (-1) bolus followed by 90 units.kg(-1).h(-1) continuous infusion). They were then allocated to receive one of three (111)In labelled antibodies: anti-D-dimer, anti-beta or a non-specific control antibody. Gamma scans of the legs were performed at regular intervals for 24 h. Scans were interpreted in a blinded fashion and the number of gamma counts from the femoral area on the thrombosed side was compared to the contralateral side. Clot/blood isotope density ratios were determined post-mortem.


RESULTS
Leg thrombi were 100% detectable in the anti-D-dimer group, but only 60% detectable in the anti-beta group. Mean +/- SD relative counts in the thrombosed femoral area was 137 +/- 10% compared to the contralateral side in the anti-D-dimer group, but only 116 +/- 20% in the anti-beta group. The clot/blood ratio was 24.5 +/- 2.8 in the anti-D-dimer group, but only 7.8 +/- 2.0 in the anti-beta group.


CONCLUSIONS
In labelled anti-D-dimer provides superior nuclear medicine images of thrombi during intensive anticoagulation compared to anti-beta. Clinical results with radiolabelled anti-D-dimer may be more promising than those previously observed with other anti-fibrin antibodies.
Department of Medicine, Division of Pulmonary/Critical Care, University of California-San Diego, UCSD Medical Center, 200 West Arbor Drive, San Diego, CA 92103-8378, USA. t1morris@ucsd.edu
Timothy A
TA
Morris
James J
JJ
Marsh
Ronald
R
Konopka
Craig A
CA
Pedersen
Peter G
PG
Chiles
D000818:Animals; D000911:Antibodies, Monoclonal; D000925:Anticoagulants / Q000627:therapeutic use; D019281:Dimerization; D004285:Dogs; D006493:Heparin / Q000627:therapeutic use*; D007089:Image Enhancement / Q000379:methods*; D007205:Indium Radioisotopes; D007518:Isoantibodies; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D018029:Rho(D) Immune Globulin; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000000981:diagnostic imaging* / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007205:Indium Radioisotopes; D007518:Isoantibodies; C061961:RHO(D) antibody; D019275:Radiopharmaceuticals; D018029:Rho(D) Immune Globulin; D006493:Heparin