Volumetric contrast-enhanced ultrasound imaging to assess early response to apoptosis-inducing anti-death receptor 5 antibody therapy in a breast cancer animal model

Kenneth Hoyt, Anna Sorace, Reshu Saini

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22 Citations (Scopus)

Abstract

Objectives-The objective of this study was to determine whether volumetric contrastenhanced ultrasound (US) imaging could detect early tumor response to anti-death receptor 5 antibody (TRA-8) therapy alone or in combination with chemotherapy in a preclinical triple-negative breast cancer animal model. Methods-Animal experiments had Institutional Animal Care and Use Committee approval. Thirty breast tumor-bearing mice were administered Abraxane (paclitaxel; Celgene Corporation, Summit, NJ), TRA-8, TRA-8 + Abraxane, or saline as a control on days 0, 3, 7, 10, 14, and 17. Volumetric contrast-enhanced US imaging was performed on days 0, 1, 3, and 7 before dosing. Changes in parametric maps of tumor perfusion were compared with the tumor volume and immunohistologic findings. Results-Therapeutic efficacy was detected within 7 days after drug administration using parametric volumetric contrast-enhanced US imaging. Decreased tumor perfusion was observed in both the TRA-8-alone- and TRA-8 + Abraxane-dosed animals compared to control tumors (P = .17; P = .001, respectively). The reduction in perfusion observed in the TRA-8 + Abraxane group was matched with a corresponding regression in tumor size over the same period. Survival curves illustrate that the combination of TRA-8 + Abraxane improves drug efficacy compared to the same drugs administered alone. Immunohistologic analysis revealed increased levels of apoptotic activity in the TRA-8-dosed tumors, confirming enhanced antitumor effects. Conclusions- Preliminary results are encouraging, and volumetric contrast-enhanced US-based tumor perfusion imaging may prove clinically feasible for detecting and monitoring the early antitumor effects in response to combination TRA-8 + Abraxane therapy.

Original languageEnglish (US)
Pages (from-to)1759-1766
Number of pages8
JournalJournal of Ultrasound in Medicine
Volume31
Issue number11
StatePublished - Nov 1 2012

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TNF-Related Apoptosis-Inducing Ligand Receptors
Ultrasonography
Animal Models
Apoptosis
Breast Neoplasms
Antibodies
Neoplasms
Perfusion
Therapeutics
Animal Care Committees
Pharmaceutical Preparations
Triple Negative Breast Neoplasms
Perfusion Imaging
Paclitaxel
Combination Drug Therapy
Tumor Burden
Albumin-Bound Paclitaxel
Research Design

Keywords

  • Antibody therapy
  • Breast cancer
  • Contrast-enhanced ultrasound
  • Microbubbles
  • Volumetric imaging

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Cite this

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title = "Volumetric contrast-enhanced ultrasound imaging to assess early response to apoptosis-inducing anti-death receptor 5 antibody therapy in a breast cancer animal model",
abstract = "Objectives-The objective of this study was to determine whether volumetric contrastenhanced ultrasound (US) imaging could detect early tumor response to anti-death receptor 5 antibody (TRA-8) therapy alone or in combination with chemotherapy in a preclinical triple-negative breast cancer animal model. Methods-Animal experiments had Institutional Animal Care and Use Committee approval. Thirty breast tumor-bearing mice were administered Abraxane (paclitaxel; Celgene Corporation, Summit, NJ), TRA-8, TRA-8 + Abraxane, or saline as a control on days 0, 3, 7, 10, 14, and 17. Volumetric contrast-enhanced US imaging was performed on days 0, 1, 3, and 7 before dosing. Changes in parametric maps of tumor perfusion were compared with the tumor volume and immunohistologic findings. Results-Therapeutic efficacy was detected within 7 days after drug administration using parametric volumetric contrast-enhanced US imaging. Decreased tumor perfusion was observed in both the TRA-8-alone- and TRA-8 + Abraxane-dosed animals compared to control tumors (P = .17; P = .001, respectively). The reduction in perfusion observed in the TRA-8 + Abraxane group was matched with a corresponding regression in tumor size over the same period. Survival curves illustrate that the combination of TRA-8 + Abraxane improves drug efficacy compared to the same drugs administered alone. Immunohistologic analysis revealed increased levels of apoptotic activity in the TRA-8-dosed tumors, confirming enhanced antitumor effects. Conclusions- Preliminary results are encouraging, and volumetric contrast-enhanced US-based tumor perfusion imaging may prove clinically feasible for detecting and monitoring the early antitumor effects in response to combination TRA-8 + Abraxane therapy.",
keywords = "Antibody therapy, Breast cancer, Contrast-enhanced ultrasound, Microbubbles, Volumetric imaging",
author = "Kenneth Hoyt and Anna Sorace and Reshu Saini",
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N2 - Objectives-The objective of this study was to determine whether volumetric contrastenhanced ultrasound (US) imaging could detect early tumor response to anti-death receptor 5 antibody (TRA-8) therapy alone or in combination with chemotherapy in a preclinical triple-negative breast cancer animal model. Methods-Animal experiments had Institutional Animal Care and Use Committee approval. Thirty breast tumor-bearing mice were administered Abraxane (paclitaxel; Celgene Corporation, Summit, NJ), TRA-8, TRA-8 + Abraxane, or saline as a control on days 0, 3, 7, 10, 14, and 17. Volumetric contrast-enhanced US imaging was performed on days 0, 1, 3, and 7 before dosing. Changes in parametric maps of tumor perfusion were compared with the tumor volume and immunohistologic findings. Results-Therapeutic efficacy was detected within 7 days after drug administration using parametric volumetric contrast-enhanced US imaging. Decreased tumor perfusion was observed in both the TRA-8-alone- and TRA-8 + Abraxane-dosed animals compared to control tumors (P = .17; P = .001, respectively). The reduction in perfusion observed in the TRA-8 + Abraxane group was matched with a corresponding regression in tumor size over the same period. Survival curves illustrate that the combination of TRA-8 + Abraxane improves drug efficacy compared to the same drugs administered alone. Immunohistologic analysis revealed increased levels of apoptotic activity in the TRA-8-dosed tumors, confirming enhanced antitumor effects. Conclusions- Preliminary results are encouraging, and volumetric contrast-enhanced US-based tumor perfusion imaging may prove clinically feasible for detecting and monitoring the early antitumor effects in response to combination TRA-8 + Abraxane therapy.

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