Accuracy and safety of 99mTc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis: A phase II study

James D. Douketis, Jeffrey S. Ginsberg, Susan Haley, Jim Julian, Miriam Dwyer, Mark Levine, Paul R. Eisenberg, Richard Smart, Wendy Tsui, Richard H White, Timothy A. Morris, Scott Kaatz, Philip C. Comp, Mark A. Crowther, Clive Kearon, Jeannine Kassis, Shannon M. Bates, Sam Schulman, Louis Desjardins, Raymond TailleferSusan M. Begelman, Mike Gerometta

Research output: Contribution to journalArticle

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Abstract

Background: The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. 99mTc-labelled DI-DD3B6/22-80B3 Fab́ fragments ( 99mTc-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 99mTc-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 99mTc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 99mTc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. 99mTc-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 99mTc-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 99mTc-DI-80B3 imaging for suspected recurrent DVT. Conclusions: 99mTc-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.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalThrombosis Research
Volume130
Issue number3
DOIs
StatePublished - Sep 2012

Fingerprint

Immunoglobulin Fab Fragments
Venous Thrombosis
Safety
Phlebography
Thrombosis
Confidence Intervals
RHO(D) antibody
fibrin fragment D
thromboview
Immunoglobulin Fragments
Urticaria
Patient Safety
Fibrin
Routine Diagnostic Tests

Keywords

  • D-dimer
  • deep vein thrombosis
  • diagnosis
  • monoclonal antibody
  • nuclear medicine imaging

ASJC Scopus subject areas

  • Hematology

Cite this

Accuracy and safety of 99mTc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis : A phase II study. / Douketis, James D.; Ginsberg, Jeffrey S.; Haley, Susan; Julian, Jim; Dwyer, Miriam; Levine, Mark; Eisenberg, Paul R.; Smart, Richard; Tsui, Wendy; White, Richard H; Morris, Timothy A.; Kaatz, Scott; Comp, Philip C.; Crowther, Mark A.; Kearon, Clive; Kassis, Jeannine; Bates, Shannon M.; Schulman, Sam; Desjardins, Louis; Taillefer, Raymond; Begelman, Susan M.; Gerometta, Mike.

In: Thrombosis Research, Vol. 130, No. 3, 09.2012, p. 381-389.

Research output: Contribution to journalArticle

Douketis, JD, Ginsberg, JS, Haley, S, Julian, J, Dwyer, M, Levine, M, Eisenberg, PR, Smart, R, Tsui, W, White, RH, Morris, TA, Kaatz, S, Comp, PC, Crowther, MA, Kearon, C, Kassis, J, Bates, SM, Schulman, S, Desjardins, L, Taillefer, R, Begelman, SM & Gerometta, M 2012, 'Accuracy and safety of 99mTc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis: A phase II study', Thrombosis Research, vol. 130, no. 3, pp. 381-389. https://doi.org/10.1016/j.thromres.2012.05.011
Douketis, James D. ; Ginsberg, Jeffrey S. ; Haley, Susan ; Julian, Jim ; Dwyer, Miriam ; Levine, Mark ; Eisenberg, Paul R. ; Smart, Richard ; Tsui, Wendy ; White, Richard H ; Morris, Timothy A. ; Kaatz, Scott ; Comp, Philip C. ; Crowther, Mark A. ; Kearon, Clive ; Kassis, Jeannine ; Bates, Shannon M. ; Schulman, Sam ; Desjardins, Louis ; Taillefer, Raymond ; Begelman, Susan M. ; Gerometta, Mike. / Accuracy and safety of 99mTc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis : A phase II study. In: Thrombosis Research. 2012 ; Vol. 130, No. 3. pp. 381-389.
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abstract = "Background: The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. 99mTc-labelled DI-DD3B6/22-80B3 Fab́ fragments ( 99mTc-DI-80B3, ThromboView{\circledR}) 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 99mTc-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 99mTc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 99mTc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. 99mTc-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 99mTc-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 99mTc-DI-80B3 imaging for suspected recurrent DVT. Conclusions: 99mTc-DI-80B3 (ThromboView{\circledR}) 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.",
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T1 - Accuracy and safety of 99mTc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis

T2 - A phase II study

AU - Douketis, James D.

AU - Ginsberg, Jeffrey S.

AU - Haley, Susan

AU - Julian, Jim

AU - Dwyer, Miriam

AU - Levine, Mark

AU - Eisenberg, Paul R.

AU - Smart, Richard

AU - Tsui, Wendy

AU - White, Richard H

AU - Morris, Timothy A.

AU - Kaatz, Scott

AU - Comp, Philip C.

AU - Crowther, Mark A.

AU - Kearon, Clive

AU - Kassis, Jeannine

AU - Bates, Shannon M.

AU - Schulman, Sam

AU - Desjardins, Louis

AU - Taillefer, Raymond

AU - Begelman, Susan M.

AU - Gerometta, Mike

PY - 2012/9

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N2 - Background: The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. 99mTc-labelled DI-DD3B6/22-80B3 Fab́ fragments ( 99mTc-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 99mTc-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 99mTc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 99mTc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. 99mTc-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 99mTc-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 99mTc-DI-80B3 imaging for suspected recurrent DVT. Conclusions: 99mTc-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.

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