Cancer remains a formidable threat to the lives of millions of Americans; one of every four deaths in the U.S. is from cancer with about 1.5 million new cases diagnosed each year. Yet, the number of deaths from common solid tumors of adults has not decreased significantly in the past 30 years. Given this history, recent studies demonstrating the potential of new drugs that target tumor blood vessel growth (angiogenesis) are particularly exciting. Now that several of these anti-angiogenic agents are entering clinical trials (e.g., endostatin) an assessment of their ability to inhibit angiogenesis is crucial for evaluating their clinical potential. Magnetic resonance imaging (MRI) with contrast agents has the potential to provide a wealth of information relevant to this goal. Yet, many of the current contrast agent methods have proved to be either nonspecific measures of angiogenesis or not clinically applicable. Thus, this research seeks to develop and validate methods that are both clinically applicable and provide angiogenic-specific measurements. We will investigate both relaxivity (T1:
Aim 1) and susceptibility (T2:
Aim 2) contrast agent methods to measure blood volume and vascular morphology. Initial method development and validation will be accomplished in a rat tumor model. Development will include characterizing the biophysical relationships underlying the contrast-agent MRI signal, an approach unique to these studies and relevant to all contrast-agent MRI methods. Taken together this information should enable the rational application of T1 and T2 contrast methods to evaluate angiogenesis in glioma patients (Aim 3), a patient population in desperate need of better therapies. Completion of these studies should move us closer to the ultimate goal of dramatically improving the diagnosis and management of patients with vascular tumors such as gliomas. Thus given the fundamental but clinically relevant nature of these studies, whose results can be applied to the study of all solid tumors, the potential impact of the proposed studies is enormous.
Showing the most recent 10 out of 54 publications
