This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 we will develop MR and optical imaging methods to predict the aggressiveness of human prostate cancer in mouse xenografts. Previously 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. In particular, low temperature NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins including FAD) fluorescence imaging or """"""""redox scanning"""""""" (translatable to biopsy specimens) 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)). Redox scanning indicated that the Fp redox ratio in the tumor core correlated significantly with the aggressiveness indices of five melanoma xenografts spanning the full range of potential to metastasis. In addition redox imaging biomarkers have been shown to differentiate between an indolent MCF-7 breast cancer mouse xenografts from an MDA-MB-231 aggressive one. T1rho-MRI is sensitive to proton exchange between water and macromolecules. Previously we have succeeded in using T1rho to differentiate three melanoma xenografts with different aggressiveness. CEST-MRI (Chemical Exchange Saturation Transfer-MRI) is a similar method also sensitive to proton exchange but with more chemical shift specificity. In this project we will employ redox scanning in combination with CEST-MRI to characterize these xenografts of prostate cancer and to identify imaging markers for tumor aggressiveness.
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