Abstract The inability to successfully treat women with ovarian cancer is due in large part to the advanced stage of disease at diagnosis, the development of platinum resistance, and the lack of sensitive methods to monitor tumor progression and response to treatment. Vascular cell adhesion molecule-1 (VCAM-1) is expressed on the mesothelium of ovarian cancer patients. We investigated VCAM-1 expression as a marker of peritoneal metastasis and tumor response to platinum-based chemotherapy. Immunohistochemical staining of peritoneal or omental biopsies obtained from women diagnosed with Stage I, Stage II or Stage III/IV ovarian cancer demonstrated that VCAM-1 expression correlated with tumor stage. All specimens from Stage I patients were negative, while 29% of Stage II patients and the 73% of Stage III/IV patients were positive. While the majority of women with advanced stage disease expressed VCAM-1, the incidence of expression was reduced among women who received neoadjuvant chemotherapy, suggesting a role for chemotherapy in regulating VCAM-1 expression. The effects of carboplatin on mesothelial VCAM-1 expression were determined in a mouse model of ovarian cancer peritoneal metastasis using radiolabeled VCAM-1-specific peptide imaging probes and single photon emission computed tomography (SPECT). This approach showed that 1) VCAM-1 is a viable imaging target in ovarian cancer metastasis, 2) maximal expression was detected with microscopic tumor burden, and 3) VCAM-1 expression reflected the effect of platinum-based treatment on tumor burden. Specifically, carboplatin treatment of mice with platinum-sensitive tumors showed reduced VCAM-1 expression, which correlated with reduced tumor burden; mice with platinum-resistant tumors retained elevated VCAM-1 expression and tumor burden following treatment. These observations support testing the utility of VCAM-1 imaging probes to monitor treatment response in ovarian cancer patients, thus providing the potential to improve management of women with this disease. Citation Format: Jill K. Slack-Davis, Jennifer M. Scalici, Stephanie Thomas, Christine Harrer, Timothy A. Raines, Joanna Curran, Kristen A. Atkins, Mark R. Conaway, Linda Duska, Kimberly A. Kelly. Imaging the tumor micro-environment to monitor ovarian cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A62.