Nanoparticle Contrast Agents: MicroCT Of Colon Cancer

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DESCRIPTION (provided by applicant): Recent advances in microCT machines have made it possible to image with a resolution of <10 fm. Scans take approximately 6 to 20 min to acquire, and current iodine agents due to their short half life are not generally suitable. We are developing gold nanoparticle contrast agents with longer residence times. This would permit in vivo visualization of organ function, angiogenesis, repair, tumor formation, metastasis, studies of response to drugs and other therapies or conditions (such as ischemia or radiation), and basic biological studies of animals including development, infection, immune response, cardiac studies, tissue injury and healing. Gold is also more absorptive than iodine, producing better contrast. For x-ray, MRI, and ultrasound, there are surprisingly few if any successful antibody or peptide targeted contrast agents. With the higher payload of nanoparticles, we anticipate this will now be possible, and we will also develop targeted contrast agents. Preliminary results show the gold nanoparticle contrast agents are soluble to 1 g Au/ml, are well tolerated in vivo at approximately 30 mg Au/ml final blood concentration, and give excellent images of internal organs for up to 30 minutes using conventional x-ray sources. Blood vessels at least as small as 100-200 microns are seen. The high solubility, low toxicity, longer blood pool residence, low liver uptake, and remarkable x-ray images are surprising properties of these new contrast agents. Colon cancer is the second leading cause of total cancer death in the US, with 48,000 deaths each year. Our studies will focus on colon cancer mouse models using microCT. In vivo virtual vascular casts will be possible, and the vascularity of a growing tumor will be followed in the same animal over time, so that local vascularity may be correlated with tumor growth in vivo at high resolution. Targeted agents will improve imaging specificity. If successful, these agents could provide: a) better patient screening to earlier detect pre-cancerous colon polyps with higher accuracy and less invasiveness, b) targeted agents to sensitively reveal tumors and metastases, c) an improved method to follow disease progression and response to therapies, d) a new tool to study and better understand colon cancer, and e) a new method to conduct studies in small animals.