Abstract 5248: A novel ovarian cancer imaging agent based on integrin ligation

Abstract

Abstract Ovarian cancer diagnosis and subsequent evaluation of disease progression is difficult due to the location of tumor mass and access to the organs affected. Ultrasound and surgical exposure are required to confirm disease and response to treatment. In an effort to develop a non-invasive radiologic method for both diagnostic assessment and to follow disease progression we have produced a integrin ligand, vicrostatin (VCN) that can be radiolabeled and imaged upon binding to active integrins over-expressed on the tumor. VCN displays a high affinity for integrins which are active and pivotal in tumor growth and progression. In the present studies we utilized an animal model employing the luciferase expressing cell line OVCAR-3luc. This procedure allows us to observe both the tumor itself in a living animal, and also co-register the PET image with the optical image enabling us to detect tumors in the intraperitoneal (IP) space. For these experiments we injected OVCAR-3luc cells IP and allowed the tumors to age for 28 days. At this point, with no obvious sign of disease, we imaged the tumors using the optical imaging system to detect the presence of luciferase. Since luciferase is only found in the tumor, this enables us to specifically image the tumor. Following these images 64Cu-DOTA-VCN is injected into the tail vein of the study animals and allowed to circulate for 90 minutes. At this time the animal is placed onto the mounting tray of the PET imaging instrument. There is a specific accumulation of 64Cu-DOTA-VCN in an area in the lower abdomen that correlates with a location of luciferase activity seen in the optical image. Both of these positions were confirmed by dissection and exposure of the tumor in the sacrificed animal. Experiments in which a larger number of cells are injected IP produced unusable optical images, as the tumors grew very large and coated much of the surface in the IP space yielding bright and indistinguishable images in the mouse abdomen. One problem of note is the high level of uptake by the kidneys at the 90 minute time point. The kidneys shield the ability to view an ovarian tumor via a dorsal or ventral total slice view. When viewed transversely, there is clear separation between the kidneys and the tumor mass which binds the 64Cu-DOTA-VCN. A three dimensional reconstruction yields a three dimensional model that can be rotated and rendered to observe the position of the tumor in relationship to the kidneys in space. These studies show that VCN can be utilized to image early stage OC and could possibly be used to monitor residual disease after surgical or therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5248. doi:1538-7445.AM2012-5248