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Volumetric Contrast‐Enhanced Ultrasound Imaging to Assess Early Response to Apoptosis‐Inducing Anti–Death Receptor 5 Antibody Therapy in a Breast Cancer Animal Model
Author(s) -
Hoyt Kenneth,
Sorace Anna,
Saini Reshu
Publication year - 2012
Publication title -
journal of ultrasound in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 91
eISSN - 1550-9613
pISSN - 0278-4297
DOI - 10.7863/jum.2012.31.11.1759
Subject(s) - medicine , contrast enhanced ultrasound , perfusion , paclitaxel , breast cancer , cancer , ultrasound , pathology , nuclear medicine , radiology
Objectives The objective of this study was to determine whether volumetric contrast‐enhanced 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 controlon days 0, 3, 7, 10, 14, and 17. Volumetric contrast‐enhanced US imaging was performedon 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.