In vivo measurement of tumor blood oxygenation by near-infrared spectroscopy: Immediate effects of pentobarbital overdose or carmustine treatment

Near-infrared (NIR) spectroscopy was used to measure blood oxygen saturation (SO2)in vivo, in normal rat brain and in subcutaneously-implanted rat 9L gliosarcoma. Changes in cranial and tumor blood SO2 were measured during lethal pentobarbital overdose. After sacrifice, SO2 of cranial blood fell rapidly to a mean of 5.0% of the pre-sacrifice values, whereas SO2 of tumor blood stabilized at a mean of 72.4% of the pre-sacrifice values. This suggests that oxygen consumption by tumor is very low compared to brain. Cranial blood had a higher SO2 than tumor blood before sacrifice (p=0.03), and a lower SO2 after sacrifice (p=0.02). The magnitude of the change in SO2 after sacrifice was greater in normal brain than in tumor (p=0.02), showing that brain tissue uses a greater proportion of the oxygen in ischemic blood than does tumor tissue.To determine the effect of carmustine (BCNU) treatment on tumor and cranial blood SO2, we compared BCNU-treated rats with sham-treated rats. Continuous NIR measurements before and immediately following treatment (ie. over 30–60 min) showed that tumor blood SO2 tended to increase after BCNU treatment, whereas SO2 tended to decrease following sham-treatment. The difference in SO2 between treated and control tumors was significant at 60 min (p=0.02). Thus BCNU treatment can potentially result in immediate increases in tumor oxygenation. The increase in treated tumor blood SO2 occurred despite the fact that there was no change in cranial blood SO2 even at day 4 following treatment. Tumor blood SO2 was inversely correlated with tumor size (p=0.001), confirming that blood is more poorly oxygenated in large tumors.

[1]  E. H. Fowler,et al.  Report of vascilitis and blindness after intracarotid injection of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU; NSC-409962) in dogs. , 1973, Cancer chemotherapy reports.

[2]  D. Groothuis,et al.  Blood flow and blood-to-tissue transport in 9L gliosarcomas: the role of the brain tumor model in drug delivery research , 1991, Journal of Neuro-Oncology.

[3]  E. Camporesi,et al.  Cerebrocortical oxygenation and ventilatory response during sustained hypoxia. , 1990, Respiration physiology.

[4]  R. Steen,et al.  31P NMR spectroscopic and near infrared spectrophotometric studies of effects of anesthetics on In vivo RIF‐1 tumors. relationship to tumor radiosensitivity , 1989, NMR in biomedicine.

[5]  D. Deen,et al.  BCNU-induced perturbations in the cell cycle of 9L rat brain tumor cells. , 1978, Cancer treatment reports.

[6]  S. Shalet,et al.  Testicular damage after chemotherapy for childhood brain tumors. , 1988, The Journal of pediatrics.

[7]  R. Tamargo,et al.  In vivo 31P nuclear magnetic resonance spectroscopy of subcutaneous 9L gliosarcoma: effects of tumor growth and treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea on tumor bioenergetics and histology. , 1988, Cancer research.

[8]  D. Bigner,et al.  Growth and Chemotherapeutic Response in Athymic Mice of Tumors Arising from Human Glioma‐derived Cell Lines , 1981, Journal of neuropathology and experimental neurology.

[9]  J N Weinstein,et al.  Neural computing in cancer drug development: predicting mechanism of action. , 1992, Science.

[10]  Toshiyuki Kitai,et al.  Quantitative detection of hemoglobin saturation in the liver with near‐infrared spectroscopy , 1993, Hepatology.

[11]  L. Ting,et al.  KHT sarcoma blood perfusion change after single-dose X-ray irradiation. , 1991, International journal of radiation biology.

[12]  C. Piantadosi,et al.  Near infrared monitoring of human skeletal muscle oxygenation during forearm ischemia. , 1988, Journal of applied physiology.

[13]  M. Graham,et al.  31P magnetic resonance spectroscopy is sensitive to tumor hypoxia: Perfusion and oxygenation of rat 9L gliosarcoma after treatment with BCNU , 1991, NMR in biomedicine.

[14]  P. Furmanski,et al.  31P-nuclear magnetic resonance studies of the effect of recombinant human interleukin 1 alpha on the bioenergetics of RIF-1 tumors. , 1989, Cancer research.

[15]  P L Ausmus,et al.  Effects of hyperthermia on blood flow and cis-diamminedichloroplatinum(II) pharmacokinetics in murine mammary adenocarcinomas. , 1992, Cancer research.

[16]  H C Charles,et al.  Evaluation of ba1112 rhabdomyosarcoma oxygenation with microelectrodes, optical spectrophotometry, radiosensitivity, and magnetic resonance spectroscopy , 1991, Magnetic resonance in medicine.

[17]  L. H. Gray,et al.  Determination of the oxyhaemoglobin dissociation curves for mouse and rat blood , 1964, The Journal of physiology.

[18]  K. Wong,et al.  Biodistribution of misonidazole and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in rats bearing unclamped and clamped 9L subcutaneous tumors. , 1989, International journal of radiation oncology, biology, physics.

[19]  J E Shook,et al.  Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans. , 1990, Journal of applied physiology.

[20]  J. LaManna,et al.  Regional Cerebral Metabolites, Blood Flow, Plasma Volume, and Mean Transit Time in Total Cerebral Ischemia in the Rat , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  間島寧興 早期アルツハイマー病におけるin vivo [31]P-Magnetic Resonance Spectroscopy , 1996 .

[22]  E. Shoubridge,et al.  Metabolic Changes in Cerebral Gliomas Within Hours of Treatment With Intra-Arterial BCNU Demonstrated by Phosphorus Magnetic Resonance Spectroscopy , 1987, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[23]  C. Kufta,et al.  Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies. , 1987, AJR. American journal of roentgenology.

[24]  B. Teicher,et al.  Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. , 1990, Science.

[25]  Dewys Wd,et al.  Report of vascilitis and blindness after intracarotid injection of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU; NSC-409962) in dogs. , 1973 .

[26]  Glaister Dh,et al.  Cerebral tissue oxygen status and psychomotor performance during lower body negative pressure (LBNP). , 1990 .

[27]  M. Tamura,et al.  Quantitative analysis of hemoglobin oxygenation state of rat brain in situ by near-infrared spectrophotometry. , 1988, Journal of applied physiology.

[28]  R G Steen,et al.  Edema and tumor perfusion: characterization by quantitative 1H MR imaging. , 1992, AJR. American journal of roentgenology.

[29]  D. Chaplin,et al.  The effect of therapy on tumour vascular function. , 1991, International journal of radiation biology.

[30]  B. Kleinschmidt-DeMasters,et al.  Intracarotid BCNU leukoencephalopathy , 1986, Cancer.

[31]  A. Terashi,et al.  Effects of fluosol-DA on brain edema, energy metabolites, and tissue oxygen content in acute cerebral ischemia. , 1990, Advances in neurology.

[32]  P. Clayton,et al.  Testicular Damage After Chemotherapy for Childhood Brain Tumors , 1988 .

[33]  A. Fox,et al.  Hemorrhagic encephalitis produced by selective non-occlusive intracarotid BCNU injection in dogs. , 1982, Journal of neurosurgery.

[34]  J. Fay,et al.  Encephalomyelopathy following high‐dose BCNU therapy , 1981 .