Abstract 2789: Magnetic resonance imaging detects perfusion and diffusion changes in response to a novel microenvironment ameliorator E7130 in a breast cancer model
Authors: Yamaguchi Masayuki , Ito Ken , Sakaguchi Kazuya , Hori Yusaku , Terada Yasuhiko , Semba Taro , Funahashi Yasuhiro , Fujii Hirofumi 
Published: September 2020

Introduction: The purpose of the present study was to evaluate the changes in breast cancer microenvironment by using high-field MRI after administration of a tumor microenvironment ameliorator E7130. Since E7130 is suggested to have a capability of remodeling tumor vasculatures and of suppressing anti-cancer associated fibroblasts (CAFs) in vivo, we hypothesized that MRI findings related to tumor perfusion and water diffusion could dynamically change in the tumors in response to E7130 treatment.

Experimental procedure: The Institutional Animal Care and Use Committee approved the experimental protocol. A human breast cancer cell line, Michigan Cancer Foundation-7 (MCF-7), was subcutaneously inoculated to female athymic nude mice. After tumor sizes reached 300 mm3 or greater, each mouse under general anesthesia underwent an MRI examination with a 9.4 tesla scanner. After apparent diffusion coefficient (ADC) mapping and dynamic contrast enhanced MRI (DCE-MRI) were performed, the mice were randomized into treatment and control groups. Either E7130 at the dose of 180 µg/kg (n = 19) or vehicle (n = 12) was intravenously administered into the mice (Day 0). On Day 2, follow-up MR examinations were performed. In randomly selected mice, the second follow-up examinations were performed on Day 5. After the completion of MRI examinations, the tumors were harvested and subjected to pathological analyses. One mouse in the vehicle control group was excluded from the analysis because of the remarkable extension of ischemic necrosis possibly due to thromboembolic occlusion in the vasculature.

Results: Tumor areas with high ADC values more than 1.1 × 10−3 mm2/sec expanded in the E7130-treated group on Day 2 (2.11 ± 1.79 times the baseline values on Day 0), which suggests that an alteration of diffusion of water molecules is likely to be increase in the E7130-treated tumor tissues. Area under the time intensity curve (AUC) from DCE-MRI data suggested the intense accumulation of contrast materials in the central part of the E7130-treated tumor tissues on Day 2 compared to that on Day 0 (954 ± 124 versus 843 ± 122 [arbitrary unit], P = 0.002). These findings suggest that blood flow may increase and extracellular extravascular space may expand during the early period after E7130 treatment. The increase number of tumor micro-vessels and shrinkage of tumor cells accompanied by the expansion of interstitial space were histologically confirmed in E7130-treated tumors. The size of tumors showed significant reduction compared to vehicle group after Day 5 of E7130 treatment.

Conclusion: MRI can detect changes in the tumor microenvironment produced by E7130 before decrease in tumor sizes becomes apparent. E7130 may affect to the tumor microenvironment closely related to increase of tumor perfusion and diffusion of water molecules in the breast cancer lesion of the MCF-7 xenograft model.

Citation Format: Masayuki Yamaguchi, Ken Ito, Kazuya Sakaguchi, Yusaku Hori, Yasuhiko Terada, Taro Semba, Yasuhiro Funahashi, Hirofumi Fujii. Magnetic resonance imaging detects perfusion and diffusion changes in response to a novel microenvironment ameliorator E7130 in a breast cancer model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2789.