Effect Of Death Receptor 6 (Dr6) Targeted Molecular Ultrasound Imaging On Detection Of Ovarian Tumors At Early Stage.

e17063 Background: Lack of an early detection test makes ovarian cancer (OVCA) a lethal malignancy. Although transvaginal ultrasound (TVUS) imaging is the currently used method its resolution cannot detect early stage OVCA. This study examined the suitability of a newly developed TVUS imaging agent targeting DR6 expressed by ovarian tumors. The goal was to examine whether DR6-targeted TVUS imaging agents bind with target and whether it improves early OVCA detection by enhancing TVUS signal intensity. Methods: DR6-targeted imaging agents were developed by conjugating anti-chicken DR6 antibodies with microbubbles. Four year old 140 White Leghorn hens (~20% hens of this age group develop spontaneous OVCA) were examined for OVCA by TVUS imaging before (pre-targeted, control) and after (targeted) IV injection of imaging agents. Enhancement in TVUS signal intensities was determined by subtracting gray scale pre-targeted intensities from targeted intensities. Hens were euthanized following imaging and TVUS prediction of OVCA was confirmed. Immunohistochemical (IHC) staining for DR6 and its association with TVUS intensities was examined. Differences in imaging intensity, IHC expression of DR6 and frequency of DR6-expressing microvessels among normal, early stage and late stage OVCA were analyzed by ANOVA and Mann-Whitney test. Results: DR6-targeted microbubbles bound with targets in the ovary and enhanced TVUS signal intensities remarkably. Of 140 hens, 24 had ovarian tumors associated with little or profuse ascites. Compared with pre-targeted, targeted imaging enhanced TVUS signal intensity significantly (P< 0.01) in hens with tumor at early (n = 10) or late stage (n = 14) OVCA. Gross examination confirmed TVUS prediction of tumors. IHC intensity of DR6-expresssion and frequency of DR6-expressing microvessels were significantly higher (P< 0.01) in hens with OVCA and confirmed the higher TVUS signal intensities (normal vs OVCA = 74X105 vs 88X105 in 20,000μm2area) in these hens. Conclusions: The results of this study suggest that DR6-targeted imaging agents enhance the resolution of TVUS imaging for early OVCA detection and will be a foundation for clinical studies. Support: DOD #W81XWH-14-1-0315