Improved Metallofullerene MRI Contrast Agent for Cancer Diagnosis

DESCRIPTION (provided by applicant): Breast cancer is the most common cancer in women with about 200,000 new cases and 40,000 deaths each year in the United States. Novel approaches for the detection of primary and metastatic breast cancers are urgently needed to increase the survival of patients. Current imaging techniques are limited in accuracy of diagnosis and staging of malignancy. Accuracy in current CT, PET, MRI and ultrasound diagnosis can be as low as 50% and a significant portion of patients are either misdiagnosed or under staged. MRI can provide both morphological and anatomical information with high spatial resolution and large penetration depth, thus a promising imaging modality for preoperative staging of breast cancer and monitoring tumor response to treatment. MRI is non-invasive and better than CT that uses x-ray radiation and nuclear imaging that uses radiolabeled agents. MRI-based cancer diagnosis without exposure to ionizing radiation will be of great interest to clinical cancer care andpublic health. However improvements in MR imaging specificity and sensitivity are needed to improve clarity and diagnostic accuracy. In this project we propose the development of a cancer biomarker-targeting metallofullerene contrast agent with very high molecular relaxivity. Metallofullerene has been demonstrated to be a better T1-weighted imaging agent than gadolinium- based chelates in a number of preclinical studies. The proposed cancer imaging agent incorporates Luna's promising Hydrochalarone contrastagent and angiogenic targeting molecules in one polymeric nanoparticle. Our goal is to develop an improved contrast agent for use with MRI in patients with malignant disease. It may be used to improve accuracy and staging of cancer malignancy, and to eliminate false positives and false negatives. The proposed preclinical study is designed to demonstrate the technical and commercial merits of this nanotechnology-enabled cancer diagnosis. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: NarrativeBreast cancer is the second leading cause of cancer-related deaths of women, and it is estimated that early 200,000 women are diagnosed with breast cancer every year. Novel approaches for the detection of primary and metastatic breast cancers are urgentlyneeded to increase the survival of patients and provide better tools to monitor tumor response to treatment. This project proposes to develop an improved magnetic resonance imaging contrast agent with high sensitivity and specificity for image-based diagnosis of breast cancer malignancy.