Enhancement of ovarian tumor detection with αvβ 3 integrin-targeted ultrasound molecular imaging agent in laying hens : A preclinical model of spontaneous ovarian cancer

Abstract

Objective: 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 integrinYtargeted molecular imaging agent in enhancing the detection of spontaneous ovarian tumor in laying hens, a preclinical model of OVCA. Methods: 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. Results: Ultrasound signal intensity was significantly (P < 0.001) higher in hens with earlystage 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 ofOVCA.Higher signal intensities fromtargeted imaging of ovarian tumorswere 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. Conclusions: 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. © 2013 by IGCS and ESGO.