title: Early therapy assessment of combined anti-DR5 antibody and carboplatin in triple-negative breast cancer xenografts in mice using diffusion-weighted imaging and (1)H MR spectroscopy.
abstract: OBJECTIVE
  To assess the early response of triple-negative breast-cancer (TNBC) following TRA-8 and carboplatin therapy using DWI and MRS in 2LMP and SUM159 mouse models.
  
  
  METHODS
  Four groups (n = 5/group) of each model were untreated or treated with carboplatin, TRA-8, and combination, respectively. DWI and MRS were applied on 0, 3, and 7 days after therapy initiation, and all tumors were collected thereafter for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. The changes in intratumoral apparent diffusion coefficient (ADC) and fat-water ratios (FWRs) were compared with tumor volume changes and apoptotic cell densities.
  
  
  RESULTS
  Mean ADC values of 2LMP and SUM159 tumors significantly increased 4 ± 4% and 37 ± 11% during 7 days of combination therapy, respectively, as compared to control groups (P < 0.05). Similarly, mean FWRs of 2LMP and SUM159 tumors significantly increased 102 ± 30% and 126 ± 52%, respectively, for 7 days of combined treatment (P < 0.05). The changes of the mean ADC values for 3 days (or FWRs for 7 days) were linearly proportional to either the mean volume changes or apoptotic cell densities in both models.
  
  
  CONCLUSIONS
  DWI and MRS assessed the early tumor response to TRA-8 and carboplatin in TNBC mouse models.
authors.affiliation: The Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Guihua
authors.initials: G
authors.lastname: Zhai
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Sarver
authors.forename: Sharon
authors.initials: S
authors.lastname: Samuel
authors.forename: Lee
authors.initials: L
authors.lastname: Whitworth
authors.forename: Heidi
authors.initials: H
authors.lastname: Umphrey
authors.forename: Denise K
authors.initials: DK
authors.lastname: Oelschlager
authors.forename: T Mark
authors.initials: TM
authors.lastname: Beasley
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C572208:TRA-8 monoclonal antibody; D016190:Carboplatin
keywords: DWI; MRS; TRA-8; carboplatin; triple-negative breast cancer