OVERALL OBJECTIVES

The goal of the Center for Non-Invasive Metabolomics is to develop and implement technologies for evaluating biomarkers to characterize diseases and monitor response to therapy. One of the most promising of these technologies is MR Metabolic Imaging. This uses hyperpolarized agents to detect changes in the biochemical processes in living tissues. The translation of this and other methodologies into the clinic requires studies to be performed in four different stages:

This brings together disease focused teams of faculty from basic research and clinical disciplines with experts in biomedical imaging, bioengineering and therapeutic sciences who are able to develop novel agents targeting the most important molecular-genetic events associated with disease and establish the most promising mechanism-based biomarkers for contributing to patient care. The Center for Non-Invasive Metabolomics provides focused effort from the UCSF School of Medicine and the top ranked UCSF School of Pharmacy. These individuals are able to prioritize the steps necessary to refine the technology, demonstrate feasibility and obtain safety data in pre-clinical models.

Once sufficient preliminary data have been obtained to support submission of exploratory INDs, initial proof of concept studies must be performed in patients. This integrates the technical expertise of imaging scientists in the Center for Non-Invasive Metabolomics with their colleagues from clinical and pharmacy specializations who have experience in performing “first in man” studies. It will also utilize the services of the Clinical Research Center, which has extensive experience in monitoring patients being treated with new chemical agents, the Drug Products Services Laboratory that will oversee the polarization process for samples injected into humans, the Regulatory Knowledge and Support Program and the Translational Technologies and Resources Program.

Although the demonstration of safety in patients is a decisive part of the development cycle, it is just the starting point for moving technology into the clinic. Obtaining acceptance of a new imaging modality requires that it have a well-defined impact upon patient care. The experience that researchers in the Center for Non Invasive Metabolomics have in the development of new diagnostic agents, imaging modalities and therapies puts them in an excellent position to establish the clinical utility of such techniques. Adding novel imaging to phase II clinical trials has proved to be an excellent strategy for doing this in a timely and cost effective manner. These studies can only be done at an institution such as UCSF, which has the diverse patient populations, imaging expertise and resources required.

The next step in establishing the utility of the technology requires a major focus from industry and government agencies to show that results from a single institution can be reproduced in a more diverse setting and in a larger population of patients. UCSF will play an advisory role in preparing for and implementing such studies. Obtaining funding for multi-center trials of new imaging modalities involves a combination of sources including private-public partnerships, participation from cooperative clinical trial groups and interaction with regulatory bodies. The Center for Non Invasive Metabolomics will contribute to this effort by drawing upon the experience of imaging scientists and physicians at UCSF who are routinely participating in multi-center clinical trials.