Microtopology of local perfusion, oxygenation, metabolic and energetic status, and interstitial pH in malignant tumors: Techniques and characterization

Experimental Oncology

Volumn 22, Issue 1-2, 2000, Pages 15-25

  Vaupel, P ^a   Kelleher, D K ^a   Thews, O ^a  

^a JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

Microtopology; Tumor metabolic status; Tumor microenvironment; Tumor oxygenation; Tumor perfusion; Tumor pH

Indexed keywords

EID: 0011026251     PISSN: 02043564     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (116)

1. Teicher BA, ed. Drug Resistance in Oncology. New York, Basel, Hongkong: Marcel Dekker, 1993.
2. Hall EJ, ed. Radiobiology for the Radiologist. 4th ed. Philadelphia: Lippincott, 1994.
3. Hoeckel M, Schlenger K, Aral B, Mitze M, Schaeffer U, Vaupel P. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 1996; 56: 4509-15.
4. Hill RP. Tumor progression: Potential role of unstable genomic changes. Cancer Metast Rev 1990; 9: 137-47.
5. Sutherland RM. Tumor hypoxia and gene expression. Implications for malignant progression and therapy. Acta Oncol 1998; 37: 567-74.
6. Sutherland RM, Ausserer WA, Murphy BJ, Laderoute KR. Tumor hypoxia and heterogeneity: Challenges and opportunities for the future. Sem Radiat Oncol 1996; 6: 59-70.
7. Royds JA, Dower SK, Qwarnstrom EE, Lewis CE. Response of tumour cells to hypoxia: role of p53 and NFkB. Mol Pathol 1998; 51: 55-61.
8. Cuvier C, Jang A, Hill RP. Exposure to hypoxia, glucose starvation and acidosis: effect on invasive capacity of murine tumor cells and correlation with cathepsin (L+B) secretion. Clin Exp Metastasis 1997; 15: 19-25.
9. Graham CH, Forsdike J, Fitzgerald CJ, MacDonald-Goodfellow S. Hypoxia-mediated stimulation of carcinoma cell invasiveness via upregulation of urokinase receptor expression. Int J Cancer 1999; 80: 617-23.
10. Hoeckel M, Schlenger K, Hoeckel S, Vaupel P. Association between tumor hypoxia and malignant progression: The clinical evidence in cancer of the uterine cervix. In: Vaupel P, Kelleher DK, eds. Tumor Hypoxia: Pathophysiology, Clinical Significance and Therapeutic Perspectives. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1999: 65-74.
11. Young SD, Marshall RS, Hill RP. Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumour cells. Proc Natl Acad Sci USA 1988; 85: 9533-7.
12. Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Ean JM, Prosnitz LR, Dewhirst MW. Tumor oxygenation predicts the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 1996; 56: 591-4.
13. Sundfor K, Lyng H, Rofstad EK. Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br J Cancer 1998; 78: 822-7.
14. Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 1997; 38: 285-9.
15. Jang A, Hill RP. An examination of the effects of hypoxia, acidosis, and glucose starvation on the expression of metastasis-associated genes in murine tumor cells. Clin Exp Metastasis 1997; 15: 469-83.
16. 2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 1993; 26: 45-50.
17. Brizel DM. Human tumor oxygenation: The Duke University Medical Center Experience. In: Vaupel P, Kelleher DK, eds. Tumor Hypoxia. Pathophysiology, Clinical Significance and Therapeutic Perspectives. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1999: 29-38.
18. Nordsmark M, Overgaard J. Oxygenation of human tumors: The Aarhus Experience. In: Vaupel P, Kelleher DK, eds. Tumor Hypoxia. Pathophysiology, Clinical Significance and Therapeutic Perspectives. Stuttgart: Wissenschaftliche Verlagsgesellschaft; 1999, 19-27.
19. Walenta S, Wetterung M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK, Mueller-Klieser W. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 2000; 60: 916-21.
20. Schwickert G, Walenta S, Sundfor K, Rofstad EK, Mueller-Klieser W. Correlation of high lactate levels in human cervical cancer with incidence of metastasis. Cancer Res 1995; 55: 4757-9.
21. Vaupel P. Pathophysiologie der Durchblutung maligner Tumoren. Funktionsanalyse biolog Systeme 1982; 8: 155-70.
22. Smits GJ, Roman RJ, Lombard JH. Evaluation of laser-Doppler flowmetry as a measure of tissue blood flow. J Appl Physiol 1986; 61: 666-72.
23. Vaupel P, Kluge M, Ambroz MC. Laser Doppler flowmetry in subepidermal tumours and in normal skin of rats during localized ultrasound hyperthermia. Int J Hyperthermia 1988; 4: 307-21.
24. Vaupel P, Okunieff P, Kluge M. Response of tumour red blood cell flux to hyperthermia and/or hyperglycaemia. Int J Hyperthermia 1989; 5: 199-210.
25. Mayer W-K, Stohrer M, Krueger W, Vaupel P. Laser Doppler flux and tissue oxygenation of experimental tumours upon local hyperthermia and/or hyperglycaemia. J Cancer Res Clin Oncol 1992; 118: 523-8.
26. Kelleher DK, Engel T, Vaupel PW. Changes in microregional perfusion, oxygenation, ATP and lactate distribution in subcutaneous rat tumours upon water-filtered IR-A hyperthermia. Int J Hyperthermia 1995; 11: 241-55.
27. Song CW, Rhee JG, Haumschild DJ. Continuous and non-invasive quantification of heat-induced changes in blood flow in the skin and RIF-1 tumour of mice by laser Doppler flowmetry. Int J Hyperthermia 1987; 3: 71-7.
28. Hill SA, Pigott KH, Saunders MI, Powell MEB, Arnold S, Obeid A, Ward G, Leahy M, Hoskin PJ, Chaplin DJ. Microregional blood flow in murine and human tumours assessed using laser Doppler microprobes. Br J Cancer 1996; 74: S260-S263.
29. Pigott KH, Hill SA, Chaplin DJ, Saunders MI. Microregional fluctuations in perfusion within human tumours detected using laser Doppler flowmetry. Radiother Oncol 1996; 40: 45-50.
30. Chaplin DJ, Hill SA. Temporal heterogeneity in microregional crythrocyte flux in experimental solid tumours. Br J Cancer 1995; 71: 1210-3.
31. Rhee JG, Eddy HA, Hong JJ, Suntharalingam M, Vaupel PW. Divergent changes of flow through individual blood vessels upon localized heating. Int J Hyperthermia 1996; 12: 757-69.
32. Liebert A, Leahy M, Maniewski R. Multichannel laser-Doppler probe for blood perfusion measurements with depth discrimination. Med Biol Eng Comput 1998; 36: 740-7.
33. Hummel M, Thews O, Kelleher DK, Vaupel P. Nicht-invasive Messung der Tumorperfusion in unterschiedlichen Gewebetiefen mittels Mehrkanal-Laser-Doppler-Technik. Strahlenther Onkol 1999; 175 (Suppl. 1): 62.
34. Sandison JC. The transparent chamber of the rabbit's ear giving a complete description of improved techniques of construction and introduction and general account of growth and behavior of living cells and tissues as seen with the microscope. Am J Anat 1928; 41: 447-72.
35. Peters W, Teixeira M, Intaglietta M, Gross JF. Microcirculatory studies in rat mammary carcinoma. I. Transparent chamber method, development of microvasculature, and pressures in tumor vessels. J Natl Cancer Inst 1980; 65: 631-42.
36. Endlich B, Reinhold HS, Gross JF, Intaglietta M. Tissue perfusion inhomogeneity during early tumor growth in rats. J Natl Cancer Inst 1979; 62: 387-95.
37. Li C-Y, Shan S, Huang Q, Braun RD, Lanzen J, Hu K, Lin P, Dewhirst MW. Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models. J Natl Cancer Inst 2000; 92: 143-7.
38. Hori K, Suzuki M, Tanda S, Saito S. Characterization of heterogeneous distribution of tumor blood flow in the rat. Jpn J Cancer Res 1991; 82: 109-17.
39. Dewhirst MW, Tso CY, Oliver R, Gustafson CS, Secomb TW, Gross JF. Morphologic and hemodynamic comparison of tumor and healing normal tissue microvasculature. Int J Radiat Oncol Biol Phys 1989; 17: 91-9.
40. Dewhirst MW, Vinuya RZ, Ong ET, Klitzman B, Rosner G, Secomb TW, Gross JF. Effects of bradykinin on the hemodynamics of tumor and granulating normal tissue microvasculature. Radiat Res 1992; 130: 345-54.
41. Reinhold HS, van den Berg-Blok AE. Hyperthermia-induced alteration in erythrocyte velocity in tumors. Int J Microcirc Clin Exp 1983; 2: 285-95.
42. Dudar TE, Jain RK. Differential response of normal and tumor microcirculation to hyperthermia. Cancer Res 1984; 44: 605-12.
43. Dewhirst MW, Oliver R, Tso CY, Gustafson C, Secomb T, Gross JF. Heterogeneity in tumor microvascular response to radiation. Int J Radiat Oncol Biol Phys 1990; 18: 559-68.
44. Baez S. An open cremaster muscle preparation for the study of blood vessels by in vivo microscopy. Microvasc Res 1973; 5: 384-94.
45. Brown NJ, Ali S, Reed MWR, Wiltrout R, Rees RC. Trafficking of activated lymphocytes into the RENCA tumour microcirculation in vivo in mice. Br J Cancer 1997; 76: 1572-8.
46. Kety SS. Theory of blood-tissue exchange and its application to measurement of blood flow. Methods Med Res 1960; 8: 223.
47. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L. Measurements of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol 1978; 234: H59-H66.
48. Tozer GM, Lewis S, Michalowski A, Aber V. The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma. Br J Cancer 1990; 61: 250-7.
49. Walenta S, Dellian M, Goetz AE, Kuhnle GEH, Mueller-Klieser W. Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours. Br J Cancer 1992; 66: 1099-102.
50. Casillas S, Dietz DW, Brand MI, Jones SC, Vladisavljevic A, Milsom JW. Perfusion to colorectal cancer liver metastates is not uniform and depends on tumor location and feeding vessel. J Surg Res 1997; 67: 179-85.
51. Durand RE, LePard NE. Contribution of transient blood flow to tumour hypoxia in mice. Acta Oncol 1995; 34: 317-323.
52. Bussink J, Kaanders JHAM, Rijken PFJW, Martindale CA, van der Kogel AJ. Multiparameter analysis of vasculature, perfusion and proliferation in human tumour xenografts. Br J Cancer 1998; 77: 57-64.
53. Bussink J, Kaanders JH, Rijken PF, Peters JP, Hodgkiss RJ, Marres HA, van der Kogel AJ. Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xcnografts: effects of carbogen and nicotinamide. Radiother Oncol 1999; 50: 173-84.
54. Hamberg LM, Kristjansen PEG, Hunter GJ, Wolf GL, Jain RK. Spatial heterogeneity in tumor perfusion measured with functional computed tomography at 0.05 μl resolution. Cancer Res 1994; 54: 6032-6.
55. Vaupel PW, Frinak S, Bicher HI. Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma. Cancer Res 1981; 41: 2008-13.
56. Dewhirst MW, Ong ET, Klitzman B, Secomb TW, Vinuya RZ, Dodge R, Brizel D, Gross JF. Perivascular oxygen tensions in a transplantable mammary tumor growing in a dorsal flap window chamber. Radiat Res 1992; 130: 171-82.
57. 2 measurement? In: Kessler M, Bruley DF, Clark LC, Luebbers DW, Silver IA, Strauss J, eds. Oxygen Supply. Muenchen: Urban & Schwarzenberg, 1973: 160-3.
58. Kessler M, Harrison DK, Hoeper J. Tissue oxygen measurement techniques. In: Baker CH, Nastuk WL, eds. Microcirculatory Technology. Orlando: Academic Press, 1986: 391-425.
59. Schneiderman G, Goldstick TK. Oxygen electrode design criteria and performance characteristics: recessed cathode. J Appl Physiol 1978; 45: 145-54.
60. Thews O, Kelleher DK, Vaupel PW. Intra- and inter-tumor variability of oxygenation: Quantification and evaluation of minimum number of electrode tracks for representative measurements. In: Vaupel PW, Kelleher DK, Guenderoth M, eds. Tumor Oxygenation. Stuttgart: Fischer, 1995: 39-47.
61. Thews O, Vaupel P. Relevant parameters for describing the oxygenation status of solid tumors. Strahlenther. Onkol. 1996; 172: 239-43.
62. Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review. Cancer Res 1989; 49: 6449-65.
63. Vaupel PW, Kelleher DK, Guenderoth M, eds. Tumor Oxygenation. Stuttgart: Fischer, 1995.
64. Vaupel P, Kelleher DK, eds. Tumor hypoxia. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1999.
65. 2 tension measurements. Cancer Res 1991; 51: 6098-102.
66. 2 tension measurements. Cancer Res 1991; 51: 3316-22.
67. Lyng H, Sundfor K, Rofstad EK. Oxygen tension in human tumours measured with polarographic needle electrodes and its relationship to vascular density, necrosis and hypoxia. Radiother Oncol 1997; 44: 163-9.
68. Thews O, Kelleher DK, Lecher B, Vaupel P. Effect of cell line and differentiation on the oxygenation status of experimental sarcomas. Adv Exp Med Biol 1997; 428: 123-8.
69. 2 saturation in tumor tissue of DS-carcinosarcoma during normoxia. Adv Exp Med Biol 1977; 94: 367-75.
70. Mueller-Klieser W, Vaupel P, Manz R, Schmidseder R. Intracapillary oxyhemoglobin saturation of malignant tumors in humans. Int J Radiat Oncol Biol Phys 1981; 7: 1397-404.
71. Wendling P, Manz R, Thews G, Vaupel P. Heterogeneous oxygenation of rectal carcinomas in humans: a critical parameter for preoperative irradiation? Adv Exp Med Biol 1984; 180: 293-300.
72. 2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Br J Cancer 1988; 57: 494-502.
73. 2 saturations. Radiat Res 1995; 141: 49-56.
74. 2 saturation measurements. Br J Cancer 1999; 79: 464-71.
75. Wilson DF, Cerniglia GJ. Localization of tumors and evaluation of their state of oxygenation by phosphorescence imaging. Cancer Res 1992; 52: 3988-93.
76. 2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nature Med 1997; 3: 177-82.
77. Torres-Filho IP, Leunig M, Yuan F, Intaglietta M, Jain RK. Noninvasive measurement of microvascular and interstitial oxygen profiles in a human tumor in SCID mice. Proc Natl Acad Sci USA 1994; 91: 2081-5.
78. Collingridge DR, Young WK, Vojnovic B, Wardman P, Lynch EM, Hill SA, Chaplin DJ. Measurement of tumor oxygenation: a comparison between polarographic needle electrodes and a time-resolved luminescence-based optical sensor. Radiat Res 1997; 147: 329-34.
79. Zilberstein J, Bromberg A, Frantz A, Rosenbach-Belkin V, Kritzmann A, Pfefermann R, Salomon Y, Scherz A. Light-dependent oxygen consumption in bacteriochlorophyll-serine-treated melanoma tumors: on-line determination using a tissue-inserted oxygen microsensor. Photochem Photobiol 1997; 65: 1012-9.
80. Gross MW, Karbach U, Groebe K, Franko AJ, Mueller-Klieser W. Calibration of misonidazole labelling by simultaneous measurement of oxygen tension and labelling density in multicellular spheroids. Int J Cancer 1995; 61: 567-73.
81. Aboagye EO, Lewis AD, Johnson A, Workman P, Tracy M, Huxham IM. The novel fluorinated 2-nitroimidazole hypoxia probe SR-4554: reductive metabolism and scmiquantitative localisation in human ovarian cancer multicellular spheroids as measured by electron energy loss spectroscopic analysis. Br J Cancer 1995; 72: 312-8.
82. Begg AC, Engelhardt EL, Hodgkiss RJ, McNally NJ, Terry NH, Wardman P. Nitroakridin 3582: a fluorescent nitroacridine stain for identifying hypoxic cells. Br J Radiol 1983; 56: 970-3.
83. Hodgkiss RJ, Parrick J, Porssa M, Stratford MRL. Bioreductive markers for hypoxic cells: 2-nitroimidazoles with biotinylated 1-substituents. J Med Chem 1994; 37: 4352-6.
84. Lord EM, Harwell L, Koch CJ. Detection of hypoxic cells by monoclonal antibody recognizing 2-nitroimidazole adducts. Cancer Res 1993; 53: 5721-6.
85. Raleigh JA, Zeman EM, Calkins DP, McEntee MC, Thrall DE. Distribution of hypoxia and proliferation associated markers in spontaneous canine tumors. Acta Oncol 1995; 34: 345-9.
86. Miller GG, Ngan-Lee J, Chapman JD. Intracellular localization of radioactively labeled misonidazole in EMT-6-tumor cells in vitro. Int J Radiat Oncol Biol Phys 1982; 8: 741-4.
87. Raleigh JA, Miller GG, Franko AJ, Koch CJ, Fuciarelli AF, Kelly DA. Fluorescence immunohistochemical detection of hypoxic cells in spheroids and tumours. Br J Cancer 1987; 56: 395-400.
88. Hodgkiss RJ, Webster L, Wilson GD. Development of bioreductive markers for tumour hypoxia. Acta Oncol 1995; 34: 351-5.
89. van Geel IP, Oppelaar H, Rijken PF, Bernsen HJ, Hagemeier NE, van der Kogel AJ, Hodgkiss RJ, Stewart FA. Vascular perfusion and hypoxic areas in RIF-1 tumours after photodynamic therapy. Br J Cancer 1996; 73: 288-93.
90. Chance B, Schoener B, Oshino R, Itshak F, Nakase Y. Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. J Biol Chem 1979; 254: 4764-71.
91. Olgin J, Connett RJ, Chance B. Mitochondrial redox changes during rest-work transition in dog gracilis muscle. Adv Exp Med Biol 1986; 200: 545-54.
92. th Annual Meeting of the International Society on Oxygen Transport to Tissue (in press).
93. Reinhold HS, Blachiewicz B, Berg-Blok A. Reoxygenation of tumours in "sandwich" chambers. Eur J Cancer 1979; 15: 481-9.
94. Constable TB, Rogers MA, Evans NT. Comparison between the oxygen removal rate and the histological structure of normal and tumour tissues. Pfluegers Arch 1978; 373: 145-51.
95. Mueller-Klieser W, Walenta S, Paschen W, Kallinowski F, Vaupel P. Metabolic imaging in microregions of tumors and normal tissues with bioluminescence and photon counting. J Natl Cancer Inst 1988; 80: 842-8.
96. Mueller-Klieser W, Walenta S. Geographical mapping of metabolites in biological tissue with quantitative bioluminescence and single photon imaging. Histochem J 1993; 25: 407-20.
97. Vaupel PW. Blood flow, oxygenation, tissue pH distribution and bioenergetic status of tumors. Berlin: Ernst Schering Research Foundation, Lecture 23; 1994.
98. Vaupel P. Physiological properties of malignant tumours. NMR Biomed 1992; 5: 220-5.
99. i. NMR Biomed 1994; 7: 128-36.
100. Fyles AW, Milosevic M, Wong R, Kavanagh M-C, Pintilie M, Sun A, Chapman W, Levin W, Manchul L, Keane TJ, Hill RP. Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol 1998; 48: 149-56.
101. 2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix. Radiother Oncol 1999; 53: 99-104.
102. Romero FJ, Mueller-Klieser W. Semiquantitative bioluminescent assay of glutathione. J Biolumin Chemilumin 1998; 13: 1-4.
103. Kuhnle GEH, Dellian M, Walenta S, Mueller-Klieser W, Goetz AE. Simultaneous high-resolution measurement of adenosine triphosphate levels and blood flow in the hamster amelanotic melanoma A-Mel-3. J Natl Cancer Inst 1992; 84: 1642-7.
104. Griffiths JR. Are cancer cells acidic? Br J Cancer 1991; 64: 425-7.
105. Newell KW, Wood P, Stratford I, Tannock I. Effects of agents which inhibit the regulation of intracellular pH on murine solid tumours. Br J Cancer 1992; 66: 311-7.
106. Gerweck LE, Rhee JG, Koutcher JA, Song CW, Urano M. Regulation of pH in murine tumor and muscle. Radiat Res 1991; 126: 206-9.
107. Schaefer C, Mayer W-K, Krueger W, Vaupel P. Microregional distributions of glucose, lactate, ATP and tissue pH in experimental tumours upon local hyperthermia and/or hyperglycaemia. J Cancer Res Clin Oncol 1993; 119: 599-608.
108. Kallinowski F, Vaupel P. Factors governing hyperthermia-induced pH changes in Yoshida sarcomas. Int J Hyperthermia 1989; 5: 641-52.
109. 31P-MRS measurements of extracellular pH of tumors using 3-amino-propylphosphonate. Am J Physiol (Cell Physiol 36) 1994; 267: C195-C203.
110. Stubbs M. Application of magnetic resonance techniques for imaging tumour physiology. Acta Oncol 1999; 38: 845-53.
111. Martin GR, Jain RK. Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy. Cancer Res 1994; 54: 5670-4.
112. Paschen W, Djuricic B, Mies G, Schmidt-Kastner R, Linn F. Lactate and pH in the brain: Association and dissociation in different pathophysiological states. J Neurochem 1987; 48: 154-9.
113. Hossmann K-A, Mies G, Paschen W, Szabo L, Dolan E, Wechsler W. Regional metabolism of experimental brain tumors. Acta Neuropathol (Berl) 1986; 69: 139-47.
114. Hossmann K-A, Linn F, Okada Y. Bioluminescence and fluoroscopic imaging of tissue pH and metabolites in experimental brain tumors of cat. NMR Biomed 1992; 5: 259-64.
115. 14C]dimethyloxazolidinedione and quantitative autoradiography. J Cerebr Blood Flow Metab 1985; 5: 369-75.
116. 14C-DMO in experimental brain tumors of rat. J Cerebr Blood Flow Metab 1985; 5: S247-S248.