Summary
The comprehensive work of both clinical and basic science colleagues has demonstrated a clear proof of concept for “in vitro discovered- in vivo validated” biomarkers in translational metabolic profiling research using magnetic resonance techniques. Major tissue metabolites (initially discovered by high-resolution in vitro techniques on cancer specimens) can be translated into in vivo protocols based on noninvasive magnetic resonance spectroscopy (MRS). Using 1H- and 31P-MRS on living animals or patients, a decrease in citrate and polyamines in prostate cancer, an increase of cholines in breast cancer, as well as a decreased NAA and an increased lactate in gliomas during cancer progression can be assessed noninvasively. MRS can be used to follow up conventional cytotoxic as well as targeted anticancer therapies, which has been extensively done in animal models of cancer. This review focuses on applications and protocol development for in vivo 1H- and 31P-MRS on small animal models as well as on larger animals in cancer research, diagnosis, and treatment.
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Gillies, R.J., and Morse, D.L. (2005) In vivo magnetic resonance spectroscopy in cancer. Ann. Rev. Biomed. Eng. 7, 287–326.
Gillies, R.J., Bhujwalla, Z.M., Evelhoch, J., Garwood, M., Neeman, M., Robinson, S.P., (2000) Application of magnetic resonance in model systems: tumor biology and physiology. Neoplasia. 2, 139–151.
Evelhoch, J., Gillies, R.J., Karzcmar, G.S., Koutcher, J.A., Maxwell, R.J., Nalcioglu, O., (2000) Application of magnetic resonance in model systems: cancer therapeutics. Neoplasia. 2, 152–165.
Glunde, K., and Serkova, N.J. (2006) Therapeutic targets and biomarkers identified in cancer choline phospholipid metabolism. Pharmacogenomics. 7, 1109–1123.
Mountford, C.E., Doran, S., Lean, C.L., and Russell, P. (1997) Cancer pathology in the year 2000. Biophys. Chem. 68, 127–135.
Howe, F.A., Barton, S.J., Cudlip, S.A., Stubbs, M., Saunders, D.E., Murphy, M., (2003) Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magn. Reson. Med. 49, 223–232.
Nelson, S.J. (2001) Analysis of volume MRI and MR spectroscopic imaging data for the evaluation of patients with brain tumors. Magn. Reson. Med. 46, 228–239.
Balmaceda, C., Critchell, D., Mao, X., Cheung, K., Pannullo, S., DeLaPaz, R.L., (2006) Multisection 1H magnetic resonance spectroscopic imaging assessment of glioma response to chemotherapy. J. Neurooncol. 76, 185–191.
Stanwell, P., Gluch, L., Clark, D., Tomanek, B., Baker, L., Giuffre, B., Lean, C., (2005) Specificity of choline metabolites for in vivo diagnosis of breast cancer using 1H-MRS at 1.5 T. Eur. Radiol. 15, 1037–1043.
Bolan, P.J., Nelson, M.T., Yee, D., and Garwood, M. (2005) Imaging in breast cancer; Magnetic resonance spectroscopy. Breast Cancer Res. 7, 149–152.
Schricker, A.A., Pauly, J.M., Kurhanewicz, J., Swanson, M., and Vigneron, D.B. (2001) Dualband spectral-spatial RF pulses for prostate MR spectroscopic imaging. Magn. Reson. Med. 46, 1079–1087.
Pucar, D., Koutcher, J.A., Shah, A., Dyke, J.P., Schwartz, L., Thaler, H., (2004) Preliminary assessment of magnetic resonance spectroscopic imaging in predicting treatment outcome in patients with prostate cancer at high risk for relapse. Clin. Prostate Cancer. 3, 174–181.
Zakian, K.L., Shuka-Dave, A., Meyers, P., Gorlick, R., Healey, J., Thaler, H.T., (2003) Identification of prognostic markers in bone marrow sarcomas using proton-decouples phosphorus magnetic resonance spectroscopy. Cancer Res. 63, 9042–9047.
Rudin, M., Beckman, N., Porszasz, R., Reese, T., Bochelen, D., and Sauter, A. (1999) In vivo magnetic resonance methods in pharmaceutical research: current status and perspective. NMR Biomed. 12, 69–97.
McPhail, L.D., Chung, Y.L., Madhu, B., Clark, S., Griffiths, J.R., Kelland, L.R., (2005) Tumor dose response to the vascular disrupting agent, 5,6-dimethylxantheone-4-acetic acid, using in vivo magnetic resonance spectroscopy. Clin. Cancer. Res. 11, 3705–3713.
Griffiths, J.R., McSheehy, P.M.J., Robinson, S.P., Troy, H., Chung, Y.L., Leek, R.D., (2002) Metabolic changes detected by in vivo magnetic resonance studies of HEPA-1 wild-type tumors and tumors deficient in hypoxia-inducible factor-1β (HIF-1β): Evidence of an anabolic role for the HIF-1 pathway. Cancer Res. 62, 688–695.
[17. Al-Saffar, N.M., Troy, H., Ramirez de Molina, A., Jackson, L.E., Madhu, B., Griffiths, J.R., (2006) Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of the choline kinase inhibitor MN58b in human carcinoma models. Cancer Res. 66, 427–434.
Griffin, J.L., Lehtimaki, K.K., Valonen, P.K., Grohn, O.H.J., Kettunen, M.I., Ula-Herttuala, S., (2003) Assignment of 1H nuclear magnetic resonance visible polyunsaturated fatty acids in BT4C gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death. Cancer Res. 63, 3195–3201, 2003.
Arias-Mendoza, F., Zakian, K., Schwartz, A., Howe, F.A., Koutcher, J.A., Leach, M.O., (2004) Methodological standardization for a multi-institutional in vivo trial of localized 31P MR spectroscopy in human cancer research. In vitro and normal volunteer studies. NMR Biomed. 17, 382–391.
Clinical Applications. Ch6 in Clinical MR Spectroscopy by Nouha Salibi and Mark Brown. Wiley-Liss (New York), 1998. P 143–186.
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This work was supported by the grants from the National Institutes of Health, S10 RR019316 and P30 CA046934.
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Serkova, N.J., Hasebroock, K., Kraft, S. (2009). Magnetic Resonance Spectroscopy of Living Tissues. In: Tainsky, M. (eds) Tumor Biomarker Discovery. Methods in Molecular Biology, vol 520. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-811-9_22
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DOI: https://doi.org/10.1007/978-1-60327-811-9_22
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