NMR Spectroscopy of Tumors

  • J. D. Glickson
  • J. P. Wehrle
  • S. S. Rajan
  • S. J. Li
  • R. G. Steen


Magnetic resonance imaging is widely employed in the clinical detection of cancer. Discrimination of tumors from surrounding normal tissues is based on differences in relaxation times, which are usually longer for tumors, and distortion of surrounding anatomy. While imaging has proven very sensitive, particularly for central nervous system tumors, it has limited specificity, making discrimination of tumors from a number of nonmalignant pathologies difficult. Efforts to improve diagnostic efficacy, via tumor-specific antibodies tagged with relaxation-enhancing agents, appear intrinsically limited by the relatively large quantities of antibodies required to produce a detectable enhancement (Lauffer 1987). These limitations have heightened interest in NMR spectroscopy, a technique that provides metabolic information potentially relevant to diagnosis and therapy.


Growth Delay Hypoxic Cell Clonogenic Cell Solenoidal Coil Hypoxic Fraction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ackerman JH, Grove TH, Wong GG, Gadian DG and Radda GK (1980) Mapping of metabolites in whole animals by P-31 NMR using surface coils. Nature 283:167–170.CrossRefGoogle Scholar
  2. 2.
    Aue WP, Bartholi E and Ernst RR (1976) Two-dimensional spectroscopy, application to nuclear magnetic resonance. J Chem Phys 64:2229–2246.CrossRefGoogle Scholar
  3. 3.
    Balaban RS, Gadian DG and Radda GK (1981) Phosphorus nuclear magnetic resonance study of the rat kidney in vivo. Kidney Intl 20:575–579.CrossRefGoogle Scholar
  4. 4.
    Bhujwalla Z, Mazwell RJ, Tozer GM and Griffiths JR (1987) The significance of changes in P-31 magnetic resonance spectra following radiotherapy in mouse tumors. Abstracts of the Sixth Annual Meeting of the Society of Magnetic Resonance in Medicine, vol. 2, p. 975.Google Scholar
  5. 5.
    Bottomley PA, Hart HR, Edelstein WA, Schenck JF, Smith IS, Leue WM Mueller OM and Bedington RW (1983) NMR imaging/spectroscopy system to study both anatomy and metabolism. Lancet 1:273–274.CrossRefGoogle Scholar
  6. 6.
    Bottomley PA, Charles C, Roemer P, Flamig D, Engeseth H, Edelstein W, Mueller O and Rezvani B (1987) human in vivo 31P 3DFT volume spectroscopic imaging revisited: new technical solutions and metabolite quantification. Works in Progress, Sixth Annual Meeting of the Society of Magnetic Resonance in Medicine, p. 8.Google Scholar
  7. 7.
    Braunschweiger PG and Schiffer LM (1986) Effect of dexamethasone on vascular function in RIF-1 tumors. Cancer Res 46:3299–3303.Google Scholar
  8. 8.
    Brown JM, Twentyman PR and Zamvil SS (1980) Response of the RIF-1 tumor In vitro and in C3H/Km mice to X-Radiation (cell survival, regrowth delay, and tumor control), chemotherapeutic agents, and activated macrophages. J. Natl Cancer Inst 64:605–611.Google Scholar
  9. 9.
    Brown TR, Kincaid BM and Ugurbil K (1982) NMR chemical shift imaging in three dimensions. Proc Natl Acad Sci. USA 79:3523–3526.CrossRefGoogle Scholar
  10. 10.
    Bryant DJ, Bailes DR, Bydder GM, Case HA, Collins AG, Cox U, Hall AS, Barman RR, Khenia S, McArthur P, Ross BD and Young IR (1987) In vivo four dimensional fourier transform 31P spectroscopy with correction for static field inhomogeneity and tissue susceptibility by 1H field mapping. Abstracts of the Sixth Annual Meeting of the Society of Magnetic Resonance in Medicine, vol. 1, p. 156.Google Scholar
  11. 11.
    Carmichael J, DeGraff WG, Gazdar AF, Minna JD and Mitchell JB (1987) Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 47:936–942.Google Scholar
  12. 12.
    Carmichael J, DeGraff WG, Gazdar AF, Minna JD and Mitchell JB (1987) Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of radiosensitivity. Cancer Res 47:943–946.Google Scholar
  13. 13.
    Cohen SM (1983) Application of nuclear magnetic resonance to the study of liver physiology and disease. Hepatology 3:738–749.CrossRefGoogle Scholar
  14. 14.
    Cohen JS and Lyon RC (1987) In: magnetic resonance of the reproductive system. Thorofare: Slack, Inc., Chapter 5.Google Scholar
  15. 15.
    Degner FL and Sutherland RM (1986) Theoretical evaluation of expected changes in oxygenation of tumors associated with different hemoglobin levels. Int J Radiat Oncol Biol Phys 12:1291–1294.CrossRefGoogle Scholar
  16. 16.
    Evanochko WT, Ng TC, Glickson JD, Durant JR and Corbett TH (1982) Human tumors as examined by in vivo 31P NMR in athymic mice. Biochem Biophys Res Commun 109:1346–1352.CrossRefGoogle Scholar
  17. 17.
    Evanochko WT, Ng TC, Lilly MB, Lawson AJ, Corbett TH, Durant JR and Glickson JD (1983) In vivo 31P NMR study of the metabolism of murine Mammary 16/C adenocarcinoma and its response to chemotherapy, X-Radiation, and Hyperthermia. Proc Natl Acad Sci. USA 80:334–338.CrossRefGoogle Scholar
  18. 18.
    Evanochko WT, Ng TC and Glickson JD (1984) Application of in vivo NMR spectroscopy to cancer. Magn Reson Med 1:508–534.CrossRefGoogle Scholar
  19. 19.
    Evanochko WT, Sakai TT, Ng TC, Krishna NR, Kim HD, Zeidler RB, Ghanta VK, Brockman RW, Schiffer IM, Braunschweiger PB and Glickson JD (1984) NMR study of RIF-1 tumors. Analysis of perchloric acid extracts and identification of 1H, 31P, and 13C resonances. Biochem Biophys Acta 805:104–116.CrossRefGoogle Scholar
  20. 20.
    Evelhoch JL, Sapareto SA, Nussbaum GH and Ackerman JH (1986) Correlations between phosphorus-31 NMR spectroscopy and oxygen-15 perfusion measurements in the REF-1 murine tumor in vivo. Radiat Res 106:122–131.CrossRefGoogle Scholar
  21. 21.
    Evelhoch JL, Keller NA and Corbett TH (1987) Response-specific adriamycin sensitivity markers provided by in vivo phosphorus-31 nuclear magnetic resonance spectroscopy in murine mammary adenocarcinomas. Cancer Res 47:3396–3401.Google Scholar
  22. 22.
    Freeman R, Mareci TH and Morris GA (1981) Weak satellite signals in high-resolution NMR spectra: Separating the wheat from the chaff. J Magn Reson 42:341–345.Google Scholar
  23. 23.
    Gadian DG, Proctor E and Williams SR (1987) Some recent applications of 1H NMR spectroscopy in vivo. Ann NY Acad Sci 508:241–250.CrossRefGoogle Scholar
  24. 24.
    Glickson JD, Evanochko WT, Sakai TT and Ng TC (1987) In vivo NMR spectroscopy of tumors. In: Gupta RK (ed) NMR spectroscopy of cells and organisms, vol. 1. Boca Raton: CRC Press pp. 99–134.Google Scholar
  25. 25.
    Griffiths JR, Cady E, Edwards RT, McCready VR, Wilkie DR and Wiltshaw E (1983) P-31 NMR studies of a human tumor in situ. Lancet 1:1435–1436.CrossRefGoogle Scholar
  26. 26.
    Hall EJ (1978) In: Radiobiology for the Radiobiologist, Second Edition. Philadelphia: Harper & Row.Google Scholar
  27. 27.
    Hesketh TR, Moore JP, Morris JH, Taylor MJ, Rogers J, Smith GA and Metcalfe JC (1985) A common sequence of calcium and pH signals in the mitogenic stimulation of eucaryotic cells. Nature 313:481–484.CrossRefGoogle Scholar
  28. 28.
    Hetherington HP, Avison MJ and Shulman RG (1985) Proton homonuclear editing of rat brain using semiselective pulses. Proc Natl Acad Sci. USA 85:3115–3118.CrossRefGoogle Scholar
  29. 29.
    Holland GA, Lenkinski RE, Allman T, Kressel HY, Charles HC, Engeseth H, Flamig D and Rezvani B (1987) Preliminary clinical experience with phosphorus-31 chemical shift imaging at 1.5 T. works in progress, Sixth Annual Meeting of the Society of Magnetic Resonance in Medicine, p. 19.Google Scholar
  30. 30.
    Hoult DI (1979) Rotating frame zeugmatography. J Magn Reson 33:183–197.Google Scholar
  31. 31.
    Hull WE, Port R, Kunz W and Schlag P (1987) 19F-NMR for monitoring 5-fluorouracil chemotherapy. Abstracts of the Sixth Annual Meeting of the Society of Magnetic Resonance in Medicine, vol. 1, p. 107.Google Scholar
  32. 32.
    Irving MG, Brooks WM, Brereton IM, Galloway GJ, Filed J, Bell OR, Harris MS, Baddeley H and Doddrell EM (1987) Use of high resolution in vivo volume selected 1H magnetic resonance spectroscopy to investigate leukemia in humans. Abstracts of the Sixth Annual Meeting of the Society of Magnetic Resonance in Medicine vol. 1, p. 152.Google Scholar
  33. 33.
    Jobsis FF (1977) Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198:1264–1267.CrossRefGoogle Scholar
  34. 34.
    Jue T (1987) Winnowing the (Carbon-13)-proton resonances in the in vivo NMR spectrum. J Magn Reson 71:532–538.Google Scholar
  35. 35.
    Knop RH, Carney EN, Chen CW, Cohen JS and Minna JD (1987) Levels of high energy phosphates in human lung cancer cell lines by 31P nuclear magnetic resonance spectroscopy. Cancer Res 7:3357–3359.Google Scholar
  36. 36.
    Laing RA, Fischbarg J and Chance B (1980) Noninvasive measurements of pyridine nucleotide fluorescence from the cornea. Invest Ophthalmol Vis Sci 19:96–102.Google Scholar
  37. 37.
    Lauffer RB (1987) Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: Theory and design. Chem Rev 87:901–927.CrossRefGoogle Scholar
  38. 38.
    Lilly MB, Katholi CR and Ng TC (1985) Direct relationship between high-energy phosphate content and blood flow in thermally treated murine tumors. J Natl Cancer Inst 75:885–889.Google Scholar
  39. 39.
    Marien AH, Segebarth C, Baleriaux D, Luyten PR and den Hollander JA (1987) Quantitative analysis of localized 31P NMR spectra of human brain tumors. Abstracts of the Sixth Annual Meeting of the Society of Magnetic Resonance in Medicine, vol. 1, p. 494.Google Scholar
  40. 40.
    Maris JM, Evans AE, McLaughlin AC, D’Angio GJ, Bolinger L, Manos H and Chance B (1985) P-31 nuclear magnetic resonance spectroscopic investigation of human neuroblastoma in situ. New England J Med 312:1500–1505.CrossRefGoogle Scholar
  41. 41.
    Martin DF, Moulder JE and Fischer JJ (1980) Tumor response endpoints in the BA1112 rat sarcoma. Br J Cancer 41:271–274.Google Scholar
  42. 42.
    Maudsley, AA, Oppelt A and Ganssen A (1979) Rapid measurement of magnetic field distributions using nuclear magnetic resonance. Siemens Res Dev Rep 8:326–331.Google Scholar
  43. 43.
    Naruse S, Higuchi T, Horikawa Y, Tanaka C, Nakamura K and Hirakawa K Radiofrequency hyperthermia with successive monitoring of its effects on tumors using NMR spectroscopy. Proc Natl Acad Sci. USA 83:8343–8347.Google Scholar
  44. 44.
    Ng TC, Evanochko WT and Glickson JD (1982) Faraday Shield for surface-coil studies of subcutaneous tumors. J Magn Reson 49:526–529.Google Scholar
  45. 45.
    Ng TC, Evancchko WT, Hiramoto RN, Ghanta VK, Lilly MB, Lawson AJ, Corbett TH, Durant JR and Glickson JD (1982) 31P NMR spectroscopy of in vivo tumors. J Magn Reson 49:271–286.Google Scholar
  46. 46.
    Ng TC, Glickson JD and Bendall MR (1984) Depth pulse sequences for surface coils: spatial localization and T1 measurements. Magn Reson Med 1:450–462.CrossRefGoogle Scholar
  47. 47.
    Ng TC and Glickson JD (1985) Shielded solenoidal probe for in vivo NMR studies of solid tumors. Magn Reson Med 2:169–175.CrossRefGoogle Scholar
  48. 48.
    Ng TC, Vijayakumar S, Majors AW, Thomas FJ, Meaney TF, Baldwin NJ and (1987) Response of a non-Hodgkin lymphoma to 60Co therapy monitored by 31P MRS in situ. Int J Radiat Oncol Biol Phys 13:1545–1551.CrossRefGoogle Scholar
  49. 49.
    Oberhaensli RD, Hilton-Jones D, Bore PJ, Hands LJ, Rampling RP and Radda GK (1986) Biochemical investigation of human tumors in vivo with phosphorus-31 magnetic resonance spectroscopy. Lancet 2:8–11.CrossRefGoogle Scholar
  50. 50.
    Okunieff PG, Koutcher JA, Gerweck L, McFarland E, Hitzig B, Urano M, Brady T, Neuringer L and Suit HD (1986) Tumor size dependent changes in a murine fibrosarcoma: use of in vivo 31P NMR for non-invasive evaluation of tumor metabolic status. Int J Radiat Oncol Biol Phys 12:793–799.CrossRefGoogle Scholar
  51. 51.
    Ordidge RJ, Connelly A and Lohman JB (1986) Image-selected in vivo spectroscopy. A new technique for spatially selective NMR spectroscopy. J Magn Reson 66:283–294.Google Scholar
  52. 52.
    Pettegrew JW, Kopp SJ, Dadok J, Minshew NJ, Feliksik JM, Glonek T and Cohen MM (1986) Chemical characterization of a prominent Phosphomonoester resonance from mammalian brain. 31P and 1H NMR analysis at 4.7 and 14.1 Tesla. J Magn Reson 67: 443–450.Google Scholar
  53. 53.
    Pettegrew JW, Kopp SJ, Minshew NJ, Glonek T, Feliksik JM, Tow JP and Cohen MM (1987) 31P Nuclear magnetic resonance studies of phosphoglyceride metabolism in developing and degenerating brain: Preliminary observations. J. Neuropath Exp. Neurol 46: 419–438.CrossRefGoogle Scholar
  54. 54.
    Pillai RP, Buescher PG, Pearse DB, Sylvester JT and Eichhorn GL (1986) Phosphorus-31 NMR spectroscopy of isolated perfused lungs. Magn Reson Med 3:467–472.CrossRefGoogle Scholar
  55. 55.
    Raleigh JA, Franko AJ, Treiber EO, Lunt JA and Allen PS (1986) Covalent binding of a fluorinated 2-nitroimidazole to EMT6 tumors in BALB/C mice: Detection by fluorine-19 nuclear magnetic resonance at 2.35 T. Int J Radiat Oncol Biol Phys 12:1243–1245.CrossRefGoogle Scholar
  56. 56.
    Rauth AM, Mohindra JK and Tannock IF (1983) Activity of mitomycin C for aerobic and hypoxic cells in vitro and in vivo. Cancer Res 43:4154–4158.Google Scholar
  57. 57.
    Reid RS, Koch CJ, Castro ME, Lunt JA, Treiber EO, Boisvert DJ and Allen PS (1985) The influence of oxygenation on the 19F spin-lattice relaxation rates of fluorosol-DA. Phys Med Biol 30:677–686.CrossRefGoogle Scholar
  58. 58.
    Rosen BR, Carter EA, Pykett IL, Buchbinder BR and Brady TJ (1985) Proton chemical shift imaging: An evaluation of its clinical potential using an in vivo fatty liver model. Radiology 154:469–472.Google Scholar
  59. 59.
    Rothman DL, Behar KL, Hetherington HP and Shulman RG (1984) Homonuclear proton double-resonance difference spectroscopy of the rat brain in vivo. Proc Natl Acad Sci. USA 81:6330–6334.CrossRefGoogle Scholar
  60. 60.
    Rothman, DL, Arias-Mendoza F, Shulman GI and Shulman RG (1984) A pulse sequence for simplifying hydrogen NMR spectra of biological tissues. J Magn Reson 60:430–436.Google Scholar
  61. 61.
    Rothman DL, Behar KL, Hetherington HP, den Hollander JA, Bendall MR, Petroff OC and Shulman RG (1985) Proton-observe/carbon-13-decouple spectroscopic measurements of lactate and glutamate in the rat brain in vivo. Proc Natl Acad Sci. USA 82:1633–1637.CrossRefGoogle Scholar
  62. 62.
    Sapirstein LA (1958) Regional blood flow by fractional distribution of indicators. Am J Physiol 193:161.Google Scholar
  63. 63.
    Schiffer IM, Braunschweiger PG, Glickson JD, Evanochko WT and Ng TC (1985) Preliminary observations on the correlation of proliferative phenomena with in vivo 31P NMR spectroscopy after tumor chemotherapy. Ann NY Acad Sci 459:270–277.CrossRefGoogle Scholar
  64. 64.
    Segebarth CM, Baleriaux DF, Arnold DL, Luyten PR and den Hollander JA (1987) MR image-guided P-31 MR spectroscopy in the evaluation of brain tumor treatment. Radiology 165:215–219.Google Scholar
  65. 65.
    Steen RG, Tamargo RJ, McGovern KA, Rajan SS, Brem H, Wehrle JP and Glickson JD (1988) In vivo 31P nuclear magnetic resonance spectroscopy of subcutaneous 9L gliosarcoma: Effects of tumor growth and treatment with l,3-Bis(2-Chloroethyl)-l-nitrosourea on tumor bioenergetics and histology. Cancer Res 48:676–681.Google Scholar
  66. 66.
    Stevens AN, Morris PG, Iles RA, Sheldon PW and Griffiths JR (1984) 5-fluorouracil metabolism monitored in vivo by fluorine-19 NMR. Br J Cancer 50:113–117.CrossRefGoogle Scholar
  67. 67.
    Sutherland RM and Franko AJ (1980) On the nature of the radiobiologically hypoxic fraction in tumors. Int J Radiat Onc Biol Phys 6:117–120.Google Scholar
  68. 68.
    Swartz HM, Chen K, Pals M, Sentjurc M and Morse PD (1986) Hypoxia-sensitive NMR contrast agents. Magn Reson Med 3:169–174.CrossRefGoogle Scholar
  69. 69.
    Tannock IF and Steel GG (1969) Quantitative techniques for study of the anatomy and function of small blood vessels in tumors. J Natl Cancer Inst 42:771–782.Google Scholar
  70. 70.
    Thulborn KR, Soffe NF and Radda GK (1981) Simultaneous in vivo measurement of oxygen utilization and high-energy phosphate metabolism in rabbit skeletal muscle by multinuclear 1H and 31P NMR. J Magn Reson 45:362–366.Google Scholar
  71. 71.
    Twentyman PR, Kallman RF and Brown JM (1979) The effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. III. Cis-Diamminedichloroplatinum. Int J Radiat Oncol Biol Phys 5:1365–1367.Google Scholar
  72. 72.
    Twentyman PR, Kallman RF and Brown JM (1979) The effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors-II. cyclophosphamide. Int J Radiat Oncol Biol Fhys 5:1425–1427.Google Scholar
  73. 73.
    Twentyman PR, Brown JM, Gray JW, Franko AJ, Scoles MA, Kallman RF and (1980) A new end point tumor model system (RIF-1) for comparison of end-point studies. J Natl Cancer Inst 64:595–604.Google Scholar
  74. 74.
    Vaupel EW, Frinak S and Bicher HI (1981) Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma. Cancer Res 41:2008–2013.Google Scholar
  75. 75.
    Wehrle JP, Li SJ, Rajan SS, Steen RG and Glickson JD (1987) 31P and 1H NMR spectroscopy of tumors in vivo: Untreated growth and response to chemotherapy. Ann NY Acad Sci 508:200–214.CrossRefGoogle Scholar
  76. 76.
    Wice BM, Trugnan G, Pinto M, Rousset M, Chevalier G, Dussaulx E, Lacroix P and Zweibaum A (1985) The intracellular accumulation of UDP-N-Acetylhexosamines is concomitant with the inability of human colon cancer cells to differentiate. J Biol Chem 260:139–146.Google Scholar
  77. 77.
    Wolf W, Albright MJ, Silver MS, Weber H, Reichardt U and Sauer R (1987) Fluorine-19 NMR spectroscopic studies of the metabolism of 5-Fluorouracil in the liver of patients undergoing chemotherapy. Magn Reson Imaging 5:165–169.CrossRefGoogle Scholar
  78. 78.
    Workman P and Twentyman PR (1982) Enhancement by electron-affinic agents of the therapeutic effects of cytotoxic agents against the KHT tumor: Structure-activity relationships. Int J Radiat Oncol Biol Phys 8:623–626.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • J. D. Glickson
  • J. P. Wehrle
  • S. S. Rajan
  • S. J. Li
  • R. G. Steen

There are no affiliations available

Personalised recommendations