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: OBJECTIVE
  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.
authors.affiliation: Department of Radiology, University of Alabama at Birmingham, G082 Volker Hall, 1670 University Blvd, Birmingham, AL 35294, USA. hoyt@uab.edu
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hoyt
authors.forename: Anna
authors.initials: A
authors.lastname: Sorace
authors.forename: Reshu
authors.initials: R
authors.lastname: Saini
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D003287:Contrast Media; D005260:Female; D005466:Fluorocarbons; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003287:Contrast Media; D005466:Fluorocarbons; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C572208:TRA-8 monoclonal antibody; C042852:perflutren