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Metabolic Changes in Cerebral Gliomas Within Hours of Treatment With Intra-Arterial BCNU Demonstrated by Phosphorus Magnetic Resonance Spectroscopy

Published online by Cambridge University Press:  18 September 2015

Douglas L. Arnold*
Affiliation:
Montreal Neurological Institute and Hospital, and the Department of Neurology and Neurosurgery, McGill University, Montreal
Eric A. Shoubridge
Affiliation:
Montreal Neurological Institute and Hospital, and the Department of Neurology and Neurosurgery, McGill University, Montreal
William Feindel
Affiliation:
Montreal Neurological Institute and Hospital, and the Department of Neurology and Neurosurgery, McGill University, Montreal
Jean-Guy Villemure*
Affiliation:
Montreal Neurological Institute and Hospital, and the Department of Neurology and Neurosurgery, McGill University, Montreal
*
Montreal Neurological Institute, 3801 University Street, 3B - Webster Pavilion, Montreal, Quebec, Canada H3A 2B4
Montreal Neurological Institute, 3801 University Street, 3B - Webster Pavilion, Montreal, Quebec, Canada H3A 2B4
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Abstract:

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A 40-year-old female with a recurrent mixed astrocytoma/oligodendroglioma was treated with intraarterial BCNU at six week intervals. Phosphorus magnetic resonance spectroscopy was performed before, and on two occasions after her third treatment.

Before treatment, phosphodiesters were 25% less than normal and intracellular pH was 7.14 (normal 6.97 ± 0.02). Eight hours following treatment phosphocreatine and phosphodiesters were reduced by ∼40% and pHi increased to 7.24. Thirty-two hours after treatment, phosphocreatine and phosphodiesters had reversed their decline, but pHi had increased further to 7.35. MRI and x-ray CT scans did not show any change during this period.

This study demonstrates that chemical changes can be observed in a glioma by magnetic resonance spectroscopy shortly after chemotherapy in a clinical setting and before changes are observable by imaging modalities. This approach evidently offers a possible means of monitoring the acute metabolic response of tumours to chemotherapy or other forms of treatment by a non-invasive repeatable quantitative method.

Type
Original Articles
Copyright
Copyright © Canadian Neurological Sciences Federation 1987

References

1.Théron, T, Villemure, J-G, Worthinton, C, et al. Superselective intracerebral chemotherapy of malignant tumour with BCNU. Neuroradiol 1986; 28: 118125.CrossRefGoogle ScholarPubMed
2.Shapiro, WR, Green, SB. Reevaluating the efficacy of intra-arterial BCNU. J Neurosurg 1987; 66: 313315.Google ScholarPubMed
3.Ordidge, RJ, Connelly, A, Lohman, JAB. Image-selected in vivo spectroscopy (ISIS). A new technique for spatially selective NMR spectroscopy. J Magn Reson 1986; 66: 283294.Google Scholar
4.Luyten, PR, Groen, JP, Arnold, DL, et al. 31PMR localized spectroscopy of human brain in situ at 1.5 Tesla. Proc Soc Reson Med 1986: 10831084.Google Scholar
5.Moon, RB, Richards, JH. Determination of intracellular pH by 31P magnetic resonance. J Biol Chem 1973; 248: 7276.CrossRefGoogle ScholarPubMed
6.Garlick, PB, Radda, GK, Seeley, PJ. Studies of acidosis in the ischaemic heart by phosphorus nuclear magnetic resonance. Biochem J 1979; 184: 547554.CrossRefGoogle ScholarPubMed
7.Glonek, T, Kopp, SJ, Kot, E, et al. P-31 nuclear magnetic resonance analysis of brain: The perchloric acid extract spectrum. J Neurochem 1982; 39: 12101219.CrossRefGoogle ScholarPubMed
8.Segebarth, C, Balériaux, D, Arnold, DL, et al. Image-guided localized 3IP MR spectroscopy of human brain tumours in situ: Effect of treatment. Radioiogy (in press).Google Scholar
9.Ng, TC, Evanochko, WT, Hiramoto, RN, et al. 31P NMR spectroscopy of in vivo tumours. J Magn Reson 1982; 49: 271286.Google Scholar
10.Evanochko, WT, Ng, TC, Glickson, JD, et al. Human tumours as examined by in vivo31P NMR in athymic mice. Biochem Biophys Res Commun 1982; 109: 13461352.CrossRefGoogle Scholar
11.Evanochko, WT, Ng, TC, Glickson, JD. Application of in vivo NMR spectroscopy to cancer. Magn Reson Med 1984; 1: 508534.CrossRefGoogle ScholarPubMed
12.Naruse, S, Hirakawa, K, Horikawa, Y, et al. Measurement of in vivo 3IP nuclear magnetic resonance spectra in neuroectodermal tumours for the evaluation of the effects of chemotherapy. Cancer Res 1985; 45: 24292433.Google Scholar
13.Griffiths, JR, Cady, E, Edwards, RHT, et al. 31P-NMR studies of a human tumour in situ. Lancet 1983; 1: 14351436.CrossRefGoogle ScholarPubMed
14.Maris, JM, Evans, AE, McLaughlin, AC, et al. 31P nuclear magnetic resonance spectroscopic investigation of human neuroblastoma in situ. New Engl J Med 1985; 312: 15001505.CrossRefGoogle ScholarPubMed
15.Roos, A, Boron, WF. Intracellular pH. Physiol Rev 1981; 61: 296421.CrossRefGoogle ScholarPubMed
16.Tyler, J L, Diksic, M, Villemure, J-G, et al. Metabolic and hemodynamic evaluation of gliomas using positron emission tomography. J Nucl Med 1987, 28: 11231133.Google ScholarPubMed
17.Arnold, D, Baleriaux, D, Segebarth, C, et al. Intracellular pH of human gliomas in vivo measured by volume-selective phosphorus magnetic resonance spectroscopy. Neurology 1987; 37 (Suppl 1): 251.Google Scholar
18.Nuccitelli, R, Heiple, JM. Summary of evidence and discussion concerning the involvement of pH, in the control of cellular functions. In: Nuccitelli, and Deamer, , eds. Intracellular pH: Its Measurement, Regulation and Utilization in Cellular Functions, Alan R Liss Ine 1982: 567586.Google Scholar
19.Ober, SS, Pardee, AB. Intracellular pH is increased after transformation of Chinese hamster embryo fibroblasts. Proc Natl Acad Sci USA 1987; 84: 27662770.CrossRefGoogle ScholarPubMed
20.Syrota, A, Castaing, M, Rougemont, D, et al. Tissue acid-base balance and oxygen metabolism in human cerebral infarction studied with positron emission tomography. Ann Neurol 1983; 14: 419428.CrossRefGoogle ScholarPubMed
21.Podo, F, Carpinelli, G, Di Vito, M, et al. NMR analyses of early metabolic alterations induced by tumour necrosis factor in murine tumours. Proc Soc Magn Reson Med 1987: p 38.Google Scholar
22.Montgomery, JA, James, K, McCaleb, GS, et al. The modes of decomposition of 1,3-bis(2-chloroethyl)-1 -nitrosourea and related compounds. J Med Chem 1967; 10: 668674.CrossRefGoogle Scholar
23.Smith, BM, Vaughan, M, Greenwood, MA, et al. Membrance and cytoplasmic changes in 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-sensitive and resistant human malignant glioma-derived cell lines. J Neuro-Oncol 1983; 1: 237248.CrossRefGoogle Scholar
24.Tyler, JL, Yamamoto, YL, Diksic, M, et al. Pharmacokinetics of superselective intra-arterial and intravenous (11C) BCNU evaluated by PET. J Nucl Med 1986; 27: 775780.Google ScholarPubMed