MR AND REDOX IMAGING OF HUMAN MELANOMA MOUSE XENOGRAFTS

University Of Pennsylvania, Philadelphia PA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most cancer patients die of metastasis. Current classification of tumors on the basis of stage and grade cannot predict accurately whether and how soon a tumor will metastasize. Within the same stage and grade, some tumors may metastasize earlier than other tumors. A biomarker of tumor metastatic potential can help physician to select proper aggressiveness of the therapeutic approaches to treat the tumor while minimizing the side effects on patients. In this project our goal is to develop MR and optical imaging methods to predict the aggressiveness of human melanomas in mouse xenografts. We have obtained a panel of five melanoma cell lines with known clinical history, their metastatic potential measured in mouse models and invasive potentials measured in vitro by the Boyden chamber method. We hope to establish some imaging biomarkers utilizing this panel of human melanomas with different levels of aggressiveness. These biomarkers can then be tested on other types of cancers such as breast, prostate, lymphoma etc and eventually translated into clinic. We have selected two MRI methods, i.e., DCE-MRI and T1[unreadable]-MRI and the low temperature NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins including FAD) fluorescence imaging or "redox scanning" (measurable on biopsy specimens) for this purpose. DCE-MRI can measure the blood perfusion and vessel permeability in the tumor. T1[unreadable]-MRI quantifies the T1[unreadable] relaxation time constants reflecting the interaction between water and macromolecules. Redox scanning can measure the in vivo mitochondrial redox states of tissues on the basis of the fluorescence signals of NADH, Fp, and Fp redox ratios (Fp/(NADH+Fp)).