Abstract PS3-03: [89Zr]-pertuzumab pet imaging reveals paclitaxel treatment efficacy is positively correlated with her2 expression in human breast cancer xenograft mouse models

Abstract

Abstract Introduction: Paclitaxel (PTX) is one of the most commonly used first-line chemotherapies in the treatment of breast cancer. However, it is reported that overall PTX response rate is between 30-60% for the treatment of metastatic breast cancer. Thus, novel discoveries of molecular mechanisms that account for ineffective response is critical in breast cancer treatment. [89Zr]-Pertuzumab (antibody that targets HER2 receptors) and 2-deoxy-2- [fluorine-18] fluoro-D-glucose ([18F]-FDG) positron emission tomography/computed tomography (PET/CT) imaging allows us to noninvasively measure the amount and heterogeneity of HER2 expression and tumor glucose metabolism. These methods are clinical translatable and can provide insight into tumor biology changes during the course of therapy. This study evaluates whether HER2 expression level is correlated with PTX treatment efficacy in controlled pre-clinical mouse models of HER2+ breast cancer. Experimental Design: BT474 (1×107), MDA-MB-361 (6×106), or MDA-MB-231 (2×106) cells were subcutaneously injected into athymic nude mice (N = 7 per cell line). When the tumor volume reached approximately 200 mm3, mice were enrolled in the study. Tumor size was measured with calipers weekly until enrolled and every 3 days after experiment started. In vivo HER2 expression level was determined by [89Zr]-Pertuzumab PET/CT imaging at one week prior to initiation of treatment and confirmed with immunohistochemistry staining. PTX (15 mg/kg) was administered via i.v. on days 0 and 3. In vivo tumor metabolism was quantified by [18F]-FDG PET/CT imaging on day 0, 3 and 6. Mean, standard deviation, sum, and frequency histogram of standard uptake value (SUV) were quantified. Tumors were harvested at day 6 for histological analysis. Hematoxylin and eosin (H&E) and cleaved caspase 3 immunohistochemistry (IHC) staining were used to determine tumor apoptosis. Pearson’s correlation and ANOVA were used as statistical analysis. Results: [89Zr]-Pertuzumab SUVmean of BT474 (HER2+) tumors were 4.9±1.5, MDA-MB-361 (HER2+) tumors were 1.4±0.2 (p<0.0001, compared with BT474), and MDA-MB-231 (HER2-) tumors were 1.1±0.4 (p<0.0001, compared with BT474). [18F]-FDG SUV sum was positively correlated with tumor volume (R2=0.1669, p=0.0250). Tumor volumes showed no significant changes during the treatment. However, normalized [18F]-FDG SUV concentration changes from day 0 to day 3 was negatively correlated with baseline [89Zr]-pertuzumab SUV concentration (R2=0.3654, p=0.05). Conclusion: Preliminary results show paclitaxel treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. [89Zr]-Pertuzumab PET/CT imaging quantitively measured HER2 expression level in vivo, and [18F]-FDG PET/CT imaging revealed the early signals of drug treatment efficacy. This discovery will help identify chemotherapy responders and potentially enhance clinical decision making. Acknowledgments: We thank funding sources American Cancer Society RSG-18-006-01-CCE and NIH NCI R01CA240589. Citation Format: Yun Lu, Adriana Massicano, Patrick Song, Meng Li, Suzanne Lapi, Anna Sorace. [89Zr]-pertuzumab pet imaging reveals paclitaxel treatment efficacy is positively correlated with her2 expression in human breast cancer xenograft mouse models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-03.