ATL: A Preclinical Model of Spontaneous Ovarian Cancer

Abstract

Because of the lack of an effective early detection test, ovarian cancer (OVCA) in most cases is detected at late stages and remains a fatal gynecological malignancy. Molecular imaging provides information on the changes associated with the development of a disease at molecular levels. Because angiogenesis is an early event in tumor development, increased expression of αvβ3 integrins by ovarian tumor-associated angiogenic microvessels provides a target for noninvasive ultrasound imaging to detect early-stage OVCA. The goal of this study was to examine the feasibility of αvβ3 integrin-targeted molecular imaging agent in enhancing the detection of spontaneous ovarian tumor in laying hens, a preclinical model of OVCA. The study was conducted in 2 phases, including a cross-sectional exploratory followed by a prospective monitoring of hens for 45 weeks with targeted ultrasound imaging. Changes in ultrasound signal intensity were determined before and after the injection of αvβ3 integrin-targeted imaging agent in hens with spontaneous OVCA. All images were digitally stored. After scanning, ovarian tissues from all hens were collected and processed for histopathologic and immunohistochemical studies. Ultrasound signal intensity was significantly (P < 0.001) higher in hens with early-stage OVCA than in normal hens and increased further in late-stage OVCA. Compared with that in normal cases, ultrasound signal intensities increased approximately 19-fold in early stage and 26-fold in late-stage OVCA. Differences in signal enhancement were not observed among different histologic subtypes of OVCA. Higher signal intensities from targeted imaging of ovarian tumors were associated with increased number of αvβ3 integrin-expressing ovarian microvessels. Prospective monitoring of hens with αvβ3 integrin-targeted imaging agent detected OVCA at early stage. These results suggest that αvβ3 integrin-targeted imaging agent enhanced the visualization of ovarian tumor-associated angiogenic microvessels in hens with early-stage OVCA and may form a foundation for clinical studies.