title: Diffusion weighted imaging evaluated the early therapy effect of tamoxifen in an MNU-induced mammary cancer rat model.
abstract: OBJECTIVE
  To assess the optimal time point of diffusion-weighted imaging (DWI) for early prognosis of breast cancer following tamoxifen therapy using a methylnitrosourea (MNU)-induced ER-positive breast-cancer model.
  
  
  METHODS
  Two groups of Sprague-Dawley rats (n = 15 for group 1; n = 10 for group 2) were used. All animals (50 days old) were intravenously injected with MNU (50 mg/kg body weight) to induce ER-positive mammary tumors. When tumors were approximately 2 cm in diameter, DWI was performed on days 0, 3, and 7, and intratumoral apparent diffusion coefficient (ADC) values were measured. Therapy started on day 0 with tamoxifen (10 mg/kg diet) and continued for 4 weeks for group 1, but only 1 week for group 2, while tumor volume was measured by caliper twice weekly. All animals of group 2 were euthanized on day 7 after imaging, and Ki-67, TUNEL, ERα, and ERβ staining were performed on tumor tissue.
  
  
  RESULTS
  DW images of MNU-induced mammary tumors were successfully obtained with minimal motion artifact. For group 1, ADC change for 3 days after therapy initiation (ADC3D) was significantly correlated with tumor-volume change until day 11, but the significant correlation between ADC change for 7 days (ADC7D) and the tumor-volume change was observed until day 18. Similarly, for group 2, either ADC7D or ADC3D was significantly correlated with the tumor-volume change, but the higher significance was observed for ADC7D. Furthermore, ADC7D was significantly correlated with apoptotic (TUNEL stained), proliferative (Ki-67 stained), and ERβ-positive cell densities, but ADC3D was not significantly correlated with any of those.
  
  
  CONCLUSIONS
  ADC7D might be a more reliable surrogate imaging biomarker than ADC3D to assess effectiveness of tamoxifen therapy for ER-positive breast cancer, which may enable personalized treatment. The significant correlation between ADC7D and ERβ-positive cell density suggests that ERβ may play an important role as a therapeutic indicator of tamoxifen.
authors.affiliation: The Department of Radiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Guihua
authors.initials: G
authors.lastname: Zhai
authors.forename: Clinton J
authors.initials: CJ
authors.lastname: Grubbs
authors.forename: Cecil R
authors.initials: CR
authors.lastname: Stockard
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Umphrey
authors.forename: T Mark
authors.initials: TM
authors.lastname: Beasley
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis* / Q000188:drug therapy*; D051381:Rats; D013629:Tamoxifen / Q000008:administration & dosage*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen