Hyperacute changes in glucose metabolism of brain tumors after stereotactic radiosurgery: a PET study.

UNLABELLED Cultured tumor cells show a marked increase in deoxyglucose uptake as early as 3 h after single high-dose irradiation, reflecting hyperacute response of the cells to noxious intervention. To evaluate the hyperacute effect of high-dose irradiation on tumor glucose metabolism in vivo, we measured 2-[18F]fluoro-2-deoxy-D-glucose (FDG) tumor uptake before and immediately after stereotactic radiosurgery. METHODS A total of 19 brain tumors (17 metastatic and 2 primary, a meningioma and a central neurocytoma) in eight patients were treated with stereotactic radiosurgery. The received dose was between 24 and 32 Gy delivered to the central target point in the tumor. FDG PET was performed within 1 wk before radiosurgery and again 4 h after treatment. The net influx constant (Ki) was calculated on a pixel-by-pixel basis using graphical analysis, and the Ki ratio of tumor to ipsilateral cerebellum was used as an index of FDG uptake of the tumor. RESULTS Eighteen of 19 irradiated tumors, all metastatic tumors and the meningioma, showed a 29.7% +/- 14.0% increase in the Ki ratio, which was significantly higher than that of nonirradiated tumors (4.1% +/- 3.6%, n = 8, P < 0.0001, analysis of variance). In metastatic tumors, an increase in the Ki ratio was significantly correlated with a decrease in the size of the irradiated tumors, as revealed by follow-up with CT or MRI (r = 0.61, P = 0.012, simple regression). The meningioma did not show a significant decrease in size, probably due to the short follow-up period. The central neurocytoma did not show any change in the Ki ratio or in tumor size. CONCLUSION Serial FDG PET could be a potential tool for predicting the outcome of radiosurgery for brain tumors by detecting hyperacute changes in tumor glucose metabolism.

[1]  Y. Yonekura,et al.  Transient increase in glycolytic metabolism in cultured tumor cells immediately after exposure to ionizing radiation: from gene expression to deoxyglucose uptake. , 1997, Radiation research.

[2]  S. Baldwin,et al.  Cellular stress induces a redistribution of the glucose transporter , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  R A Hawkins,et al.  PET cancer evaluations with FDG. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  B. Vogelstein,et al.  Participation of p53 protein in the cellular response to DNA damage. , 1991, Cancer research.

[5]  W. Vaalburg,et al.  Radiation-induced inhibition of tumor growth as monitored by PET using L-[1-11C]tyrosine and fluorine-18-fluorodeoxyglucose. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  Otto Warburn,et al.  THE METABOLISM OF TUMORS , 1931 .

[7]  T G Turkington,et al.  Performance characteristics of a whole-body PET scanner. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  M. Phelps,et al.  Quantitating tumor glucose metabolism with FDG and PET. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  C. Purdie,et al.  Thymocyte apoptosis induced by p53-dependent and independent pathways , 1993, Nature.

[10]  G. van Kaick,et al.  Fluorodeoxyglucose uptake in vitro: aspects of method and effects of treatment with gemcitabine. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[11]  S. Baldwin,et al.  Cellular Stress Causes Accumulation of the Glucose Transporter at the Surface of Cells Independently of their Insulin Sensitivity , 1996, The Journal of Membrane Biology.

[12]  M. Mehta,et al.  Early changes in tumor metabolism after treatment: the effects of stereotactic radiotherapy. , 1991, International journal of radiation oncology, biology, physics.

[13]  K. Winston,et al.  A system for stereotactic radiosurgery with a linear accelerator. , 1986, International journal of radiation oncology, biology, physics.

[14]  D. Boothman,et al.  Immediate X-ray-inducible responses from mammalian cells. , 1994, Radiation research.

[15]  C. Patlak,et al.  Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[16]  W Schlegel,et al.  Cerebral radiation surgery using moving field irradiation at a linear accelerator facility. , 1985, International journal of radiation oncology, biology, physics.

[17]  I Kapouleas,et al.  Registration of three-dimensional MR and PET images of the human brain without markers. , 1991, Radiology.

[18]  G Lucignani,et al.  Measurement of regional cerebral glucose utilization with fluorine-18-FDG and PET in heterogeneous tissues: theoretical considerations and practical procedure. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  J M Hoffman,et al.  Clinical application of PET for the evaluation of brain tumors. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  C S Patlak,et al.  Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data , 1983, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  R. Weichselbaum,et al.  Ionizing radiation down-regulates histone H1 gene expression by transcriptional and post-transcriptional mechanisms. , 1993, Radiation research.

[22]  M. Mehta,et al.  Acute changes in glucose uptake after treatment: the effects of carmustine (BCNU) on human glioblastoma multiforme , 2005, Journal of Neuro-Oncology.

[23]  O. Warburg On the origin of cancer cells. , 1956, Science.

[24]  J. Hickman Apoptosis as a therapeutic target , 1996 .

[25]  H. Müller-Gärtner,et al.  Early changes in fluorine-18-FDG uptake during radiotherapy. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[26]  Scott W. Lowe,et al.  p53 is required for radiation-induced apoptosis in mouse thymocytes , 1993, Nature.

[27]  T. Nonaka,et al.  Rapid rise in FDG uptake in an irradiated human tumour xenograft , 1997, European Journal of Nuclear Medicine.

[28]  K. Hamacher,et al.  Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. , 1986, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[29]  David J. Yang,et al.  Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.