Abstract
Cancer was an obvious disease to study by magnetic resonance spectroscopy (MRS); it produces large lesions that give clearly abnormal spectra, all treatment methods leave much to be desired, and radiotherapy, in particular, is limited by tissue hypoxia, a process that can be investigated by MRS.31P MRS has shown that tumor cells are not acidic, as had been thought; instead, the pH gradient across the tumor cell membrane is the reverse of that in a normal cell. This change in hydrogen-ion gradient is accompanied by changes in gradients of many other ions.
Tumor oxygenation can be monitored in animal tumor models using the techniques employed for functional magnetic resonance imaging (MRI) of the brain. Large changes in signal are observed when drugs that reduce tumor blood flow are administered.
1H NMR spectra of acid extracts of tumor or normal tissue biopsies contain sufficient information to permit classification (and thus, perhaps, diagnosis) if computer-based pattern recognition techniques are employed. Surprisingly, the same technique gives quite good classification of31P spectra takenin vivo.
Can MRS beappliedin cancer therapy? Studies on tumor ion balance will help in the design of anticancer drugs and other therapies. Tumor blood flow studies using MRI could be applied to individual patients to predict the usefulness of radiotherapy and to assist in radiotherapy planning. Pattern recognition methods could automate the screening of biopsies and could also assist in interpretation of human spectra takenin vivo.
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References
Griffiths JR, Stevens AN, Iles RA, Gordon RA, Shaw D (1981)31P NMR investigation of solid tumours in the living rat.Biosci Rep 1 177–182.
Griffiths JR, Cady E, Edwards RHT, McCready VR, and Wiltshaw E (1983)13P NMR studies of a human tumourin situ.Lancet 1 1436–1437.
Griffiths JR (1991) Are cancer cells acidic?Br J Cancer 64 425–427.
Gillies RJ, Lui Z, Bhujwalla Z (1994)31P NMR measurement of extracellular pH of tumours and tumour cellsin vitro using 3-aminopropylphosphonate.Am J Physiol Cell 267 C195-C203.
Stubbs M, Rodrigues L, Howe FA, Wang J, Jeong K-S, Veech RL, Griffiths JR (1994) The metabolic consequences of a reversed pH gradient in rat tumours.Cancer Res 54 4011–4016.
Stubbs M, Bhujwalla ZM, Tozer GM, Rodrigues LM, Maxwell RJ, Morgan R, Howe FA, Griffiths JR (1992) An assessment of31P MRS as a method of measuring pH in rat tumours.NMR Biomed 5 351–359.
Mattiello J, and Evelhoch JL (1991) Relative volume-average murine tumor blood flow measurement via deuterium nuclear magnetic resonance spectroscopy.Magn Reson Med 18 320–334.
Tozer GM, Maxwell RJ, Griffiths JR, Pham P (1990) Modification of the31P magnetic resonance spectra of a rat tumour using vasodilators and its relationship to hypertension.Br J Cancer 39 857–863.
Burney IA, Maxwell RJ, Griffiths JR, Field SB (1991) The potential for prazosin and calcitonin gene-related (CGRP) in causing hypoxia in tumours.Br J Cancer 64 683–688.
Field SB, Needham S, Burney IA, Maxwell RJ, Coggle JE, Griffiths JR (1991) Differences in vascular response between primary and transplanted tumours.Br J Cancer 63 723–726.
Wood PJ, Stratford IJ, Sansom JM, Cattanach BM, Quinney RM, Adams GE (1992) The response of spontaneous and transplantable murine tumors to vasoactive agents measured by31P magnetic resonance spectroscopy.Int J Radiat Oncol Biol Phys 22 473–476.
Robinson SP, van den Boogaart A, Hamilton E, Waterton JC, Griffiths JR (1994) Differences in vascular response between early and late generation transplanted tumours Proceedings 2nd Meeting, Society of Magnetic Resonance, p 1336, 1994.
Howe FA, Robinson SP, Griffiths JR (1993) Monitoring changes in oxygenation and blood perfusion of a subcutaneous tumour by functional MRIProceedings 12th Annual Meeting. Society for Magnetic Resonance in Medicine, p. 1002.
Griffiths JR, Howe FA, Robinson SP (1994) Changes in tumour perfusion and oxygenation monitored by physiological MRI.Br J Cancer 69 53.
Howells SL, Maxwell RJ, Griffiths JR (1992) Classification of tumour 1H spectra by pattern recognition.NMR Biomed 5 59–64.
Howells SL, Maxwell RJ, Griffiths JR (1992) An investigation of tumor1H nuclear magnetic resonance spectra by the application of chemometric techniques.Magn Reson Med 28 214–236.
Howells SL, Maxwell RJ, Howe FA, Peet AC, Stubbs M, Rodrigues LM, Robinson SP, Baluch S, Griffiths JR (1993) Pattern recognition of31P magnetic resonance spectra obtainedin vivo.NMR Biomed 6 237–241.
Negendank W (1992) Studies of human tumors of MRS: a review.NMR Biomed 5 303–324.
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Griffiths, J.R., Maxwell, R.J., Howells, S.L. et al. MRS studies of cancer. MAGMA 2, 253–257 (1994). https://doi.org/10.1007/BF01705249
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DOI: https://doi.org/10.1007/BF01705249