Accuracy and safety of (99m)Tc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis: a phase II study.
BACKGROUND
The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. (99m)Tc-labelled DI-DD3B6/22-80B3 Fab´ fragments ((99m)Tc-DI-80B3, ThromboView®) is a novel diagnostic test that uses a radiolabelled humanized monoclonal antibody fragment specific for the D-dimer region of cross-linked fibrin to detect DVT. This test has an anatomic component to locate DVT and a functional component to differentiate acute (newly formed) thrombus from inactive (old) thrombus.


METHODS
In a multi-centre prospective cohort trial we investigated the diagnostic accuracy and safety of (99m)Tc-DI-80B3 in consecutive patients with suspected DVT who had the diagnosis confirmed or excluded by venography.


RESULTS
We enrolled 94 patients with suspected DVT of whom 12 did not have (99m)Tc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 (99m)Tc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. (99m)Tc-DI-80B3 imaging was well-tolerated: 2 patients developed urticaria; none developed serious adverse events. For proximal DVT, the sensitivity (84.2%; 95% confidence interval [CI]: 62.4-94.5) and specificity (97.6%; CI: 83.3-99.4) were highest when the combined 0.25-hour and 3-hour (99m)Tc-DI-80B3 images were used. The accuracy was lower for distal DVT, irrespective of the images used. There were insufficient patients to comment on the accuracy of (99m)Tc-DI-80B3 imaging for suspected recurrent DVT.


CONCLUSIONS
(99m)Tc-DI-80B3 (ThromboView®) is a novel diagnostic modality for patients with suspected DVT with a promising accuracy and safety profile that justifies additional clinical development in diagnostic accuracy and clinical management studies.
Dept. of Medicine, McMaster University, Hamilton, ON, Canada. jdouket@mcmaster.ca
James D
JD
Douketis
Jeffrey S
JS
Ginsberg
Susan
S
Haley
Jim
J
Julian
Miriam
M
Dwyer
Mark
M
Levine
Paul R
PR
Eisenberg
Richard
R
Smart
Wendy
W
Tsui
Richard H
RH
White
Timothy A
TA
Morris
Scott
S
Kaatz
Philip C
PC
Comp
Mark A
MA
Crowther
Clive
C
Kearon
Jeannine
J
Kassis
Shannon M
SM
Bates
Sam
S
Schulman
Louis
L
Desjardins
Raymond
R
Taillefer
Susan M
SM
Begelman
Mike
M
Gerometta
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000276:immunology; D007553:Isotope Labeling; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000276:immunology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020246:Venous Thrombosis / Q000000981:diagnostic imaging* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005338:Fibrin Fibrinogen Degradation Products; D007140:Immunoglobulin Fab Fragments; D019275:Radiopharmaceuticals; C036309:fibrin fragment D