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Diffusion weighted imaging evaluated the early therapy effect of tamoxifen in an MNU-induced mammary cancer rat model.

Authors: Zhai, G  Grubbs, CJ  Stockard, CR  Umphrey, HR  Beasley, TM  Kim, H 
Citation: Zhai G, etal., PLoS One. 2013 May 21;8(5):e64445. doi: 10.1371/journal.pone.0064445. Print 2013.
Pubmed: (View Article at PubMed) PMID:23700476
DOI: Full-text: DOI:10.1371/journal.pone.0064445

PURPOSE: 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, ERalpha, and ERbeta 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 ERbeta-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 ERbeta-positive cell density suggests that ERbeta may play an important role as a therapeutic indicator of tamoxifen.

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RGD Object Information
RGD ID: 7364946
Created: 2013-10-14
Species: All species
Last Modified: 2013-10-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.