Better tumor imaging methods are needed both for early diagnosis and for monitoring the effects of therapeutic interventions. Among various imaging strategies under development, a very promising category is based on markers present on the surface of the endothelial cells (ECs) that constitute the walls of the tumor blood vessels. A number of tumor EC markers have been reported in recent years but none proved so far good enough for large scale clinical use. We discovered recently a new tumor EC marker that is present in all tumor human tumor types analyzed, both early and advanced, and absent from all normal tissues except some areas of the gonads. Based on the information we have so far, this marker could be a better imaging target than any of the currently available. This project is aimed at demonstrating that the marker can be used for near infrared and magnetic resonance imaging (MRI) of tumors in mouse cancer models.
The first aim consists in the synthesis and characterization of nanoparticulate imaging agents and their testing in cell cultures. The nanoparticles consist of an iron oxide core oil-in-water emulsion, which can be used for both targeted imaging and for delivery of anticancer drugs. The particles will be chemically coupled to antibodies against the EC surface marker and will be characterized in terms of physical properties. The ability of the nanoparticles to bind to the marker expressed by cells in culture and generate fluorescence and MRI signals will be also verified.
The second Aim i s to test the targeted contrast agents in nude mice that carry tumors that develop after injection of human tumor cells. The agents will be delivered by i.v. injection. The proposed targeted imaging procedures are intended to constitute the basis for subsequent clinical trials. The proposed imaging strategy has the potential to lead to a general procedure for early detection of the majority of solid cancers, independently of their type and location, by a single whole-body imaging scan.
We propose to develop a new magnetic resonance imaging (MRI) agent, targeted to tumors by a newly discovered tumor marker that is present on the surface of the blood vessels in most human tumor types and absent from normal tissues. The project has the potential to introduce a general screening procedure that would allow the detection, in a single session and using a single imaging agent, of most tumor types, independently of their location in the body, and at an early stage, when anticancer therapies have much higher chances of success.
|Zhao, Yiming; van Rooy, Inge; Hak, Sjoerd et al. (2013) Near-infrared fluorescence energy transfer imaging of nanoparticle accumulation and dissociation kinetics in tumor-bearing mice. ACS Nano 7:10362-70|