Abstract

To evaluate intraperitoneal (IP) tumor engraftment, metastasis and growth in a pre-clinical murine epithelial ovarian cancer (EOC) model using both transabdominal ultrasound (TAUS) and bioluminescence in vivo imaging system (IVIS). Ten female C57Bl/6J mice at six weeks of age were included in this study. Five mice underwent IP injection of 5x106 ID8-luc cells (+ D- luciferin) and the remaining five mice underwent IP injection of ID8-VEGF cells. Monitoring of tumor growth and ascites was performed weekly starting at seven days post-injection until study endpoint. ID8-luc mice were monitored using both TAUS and IVIS, and ID8-VEGF mice underwent TAUS monitoring only. Individual tumor implant dimension and total tumor volume were calculated. Average luminescent intensity was calculated and reported per mouse abdomen. Tumor detection was confirmed by gross evaluation and histopathology. All data are presented as mean +/- standard deviation. Overall, tumors were successfully detected in all ten mice using TAUS and IVIS, and tumor detection correlated with terminal endpoint histology/ H&E staining. For TAUS, the smallest confirmed tumor measurements were at seven days post-injection with mean long axis of 2.23mm and mean tumor volume of 4.17mm3. However, IVIS imaging was able to detect tumor growth at 14 days post-injection. Ascites formation was detected in mice at 21 days post-injection. TAUS is highly discriminatory for monitoring EOC in pre-clinical murine model, allowing for detection of tumor dimension as small as 2 mm and as early as seven days post-injection compared to IVIS. In addition, TAUS provides relevant information for ascites development and detection of multiple small metastatic tumor implants. TAUS provides an accurate and reliable method to detect and monitor IP EOC growth in mouse xenografts.

Highlights

  • Epithelial ovarian cancer (EOC) is a leading cause of gynecologic cancer related mortality in women [1]

  • Tumors were successfully detected in all ten mice using transabdominal ultrasound (TAUS) and in vivo imaging system (IVIS), and tumor detection correlated with terminal endpoint histology/ H&E staining

  • For TAUS, the smallest confirmed tumor measurements were at seven days post-injection with mean long axis of 2.23mm and mean tumor volume of 4.17mm3

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Summary

Introduction

Epithelial ovarian cancer (EOC) is a leading cause of gynecologic cancer related mortality in women [1]. The five-year overall survival for women with EOC is poor since the majority of patients present with advanced and metastatic disease [2]. Patients initially respond well to treatment with surgery and chemotherapy with carboplatin and paclitaxel, the vast majority of women will recur [4,5,6,7,8]. Ovarian carcinomas primarily undergo peritoneal dissemination, and are often associated with malignant ascites. This pattern of spread is associated with vague symptoms which leads to delays in diagnosis [3]. There is a significant unmet need for methods to facilitate early diagnosis of EOC and advance current therapeutic options

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