Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer

Abstract

Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

Ultrasound molecular imaging as a non-invasive companion diagnostic for netrin-1 interference therapy in breast cancer

“…Our in vitro and in vivo data show that netrin-1, although described as a secreted and diffusible protein, bound to the cell surface and/or extracellular matrix. This observation is in line with previous reports about USMI of secreted frizzled related protein 2, interleukin 16, and GPIIb/IIIa in tumors, and confirms the feasibility of USMI in settings where free-circulating proteins can potentially saturate MBs and prevent immobilization 22 , 48 , 49 . Inter- and intra-tumoral heterogeneity with regard to vascular perfusion rates and functionality of the vascular network are crucial factors for USMI with micrometer-sized contrast agents that are injected and limited to the blood vessels 50 , 51 .…”

Efficient Source of Cells in Proximal Oviduct for Testing Non-Viral Expression Constructs in the Chicken Bioreactor Model and for Other <I>in Vitro</I> Studies

“…Many authors find clear indications that the oviduct of a laying hen might resemble malignancies occurring in the female reproductive tract. Thus, an oviduct model is highly applicable in studies on the genesis of a serous type of ovarian cancer in women (JOHNSON 2014), research on cancer stem cell markers (PAIK et al 2012) and development of tools for its diagnosis or treatment (BARUA et al 2015;LIM et al 2015). However, certain issues need to be resolved to increase the effectiveness and quality of such studies.…”

Six‐Transmembrane Epithelial Antigen of the Prostate‐1 (STEAP‐1)–Targeted Ultrasound Imaging Microbubble Improves Detection of Prostate Cancer In Vivo

“…To more improve contrast‐enhanced visualization, targeted microbubbles have been generated that actively bind molecular markers expressed on the targeted tissue . Many studies have also shown that the enhancement effect of targeted microbubbles was significantly better than ordinary microbubbles . Sanna et al reported first that the prostate‐specific membrane antigen target microbubble was successfully synthesized and could be used for PCa diagnosis.…”