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Published in: Strahlentherapie und Onkologie 11/2015

01-11-2015 | Original Article

Spatial oxygenation profiles in tumors during normo- and hyperbaric hyperoxia

Authors: Prof. Dr. med. Oliver Thews, Prof. Dr. Peter Vaupel

Published in: Strahlentherapie und Onkologie | Issue 11/2015

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Abstract

Background

Inspiratory hyperoxia reduces tumor hypoxia, which is responsible for limited radiosensitivity of tumors. However, very little is known about the heterogeneity of intratumoral oxygenation during this supportive treatment. The study analyzes whether local hypoxia is still present during normobaric and hyperbaric inspiratory hyperoxia and whether the addition of CO2 to the inspiratory gas affects the spatial pO2 distribution.

Material and methods

Tumor oxygenation of experimental DS-sarcomas in rats was assessed by polarographic needle electrodes at 1 and 2 atm (bar) environmental pressure during pure O2 or carbogen (95 % O2 + 5 % CO2) breathing. Up to 320 individual pO2 measurements were performed in a strictly oriented grid resulting in an oxygenation profile in a horizontal tumor layer.

Results

In the experimental tumors used the oxygenation showed pronounced heterogeneities with closely adjacent hypoxic and oxygenated regions. This heterogeneity was still visible under normobaric hyperoxia where large confluent hypoxic regions were detectable. At 1 atm, the addition of CO2 improved tumor oxygenation significantly (at least in large tumors). At 2 atm, only very small local regions of hypoxia were detected. However, under this condition hypercapnia had no impact on tumor oxygenation.

Conclusions

The data show that even under hyperbaric hyperoxia, hypoxic regions are detectable despite the average pO2 increased by a factor of 100. The results also clearly indicate that the oxygenation pattern improves disproportionally with increasing environmental pressure.
Literature
1.
go back to reference Hoskin PJ, Rojas AM, Saunders MI et al (2009) Carbogen and nicotinamide in locally advanced bladder cancer: early results of a phase-III randomized trial. Radiother Oncol 91:120–125CrossRefPubMed Hoskin PJ, Rojas AM, Saunders MI et al (2009) Carbogen and nicotinamide in locally advanced bladder cancer: early results of a phase-III randomized trial. Radiother Oncol 91:120–125CrossRefPubMed
2.
go back to reference Janssens GO, Bockel LW van, Doornaert PA et al (2014) Computed tomography-based tumour volume as a predictor of outcome in laryngeal cancer: results of the phase 3 ARCON trial. Eur J Cancer 50:1112–1119CrossRefPubMed Janssens GO, Bockel LW van, Doornaert PA et al (2014) Computed tomography-based tumour volume as a predictor of outcome in laryngeal cancer: results of the phase 3 ARCON trial. Eur J Cancer 50:1112–1119CrossRefPubMed
3.
go back to reference Thews O, Kelleher DK, Vaupel P (2002) Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory hyperoxia combined with different levels of inspiratory hypercapnia. Radiother Oncol 62:77–85CrossRefPubMed Thews O, Kelleher DK, Vaupel P (2002) Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory hyperoxia combined with different levels of inspiratory hypercapnia. Radiother Oncol 62:77–85CrossRefPubMed
4.
go back to reference Janssens GO, Rademakers SE, Terhaard CH et al (2014) Improved recurrence-free survival with ARCON for anemic patients with laryngeal cancer. Clin Cancer Res 20:1345–1354CrossRefPubMed Janssens GO, Rademakers SE, Terhaard CH et al (2014) Improved recurrence-free survival with ARCON for anemic patients with laryngeal cancer. Clin Cancer Res 20:1345–1354CrossRefPubMed
5.
go back to reference Rademakers SE, Hoogsteen IJ, Rijken PF et al (2015) Prognostic value of the proliferation marker Ki-67 in laryngeal carcinoma: results of the accelerated radiotherapy with carbogen breathing and Nicotinamide phase III randomized trial. Head Neck 37:171–176CrossRefPubMed Rademakers SE, Hoogsteen IJ, Rijken PF et al (2015) Prognostic value of the proliferation marker Ki-67 in laryngeal carcinoma: results of the accelerated radiotherapy with carbogen breathing and Nicotinamide phase III randomized trial. Head Neck 37:171–176CrossRefPubMed
6.
go back to reference Hoskin PJ, Rojas AM, Phillips H et al (2005) Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide. Cancer 103:2287–2297CrossRefPubMed Hoskin PJ, Rojas AM, Phillips H et al (2005) Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide. Cancer 103:2287–2297CrossRefPubMed
7.
go back to reference Becker A, Kuhnt T, Liedtke H et al (2002) Oxygenation measurements in head and neck cancers during hyperbaric oxygenation. Strahlenther Onkol 178:105–108CrossRefPubMed Becker A, Kuhnt T, Liedtke H et al (2002) Oxygenation measurements in head and neck cancers during hyperbaric oxygenation. Strahlenther Onkol 178:105–108CrossRefPubMed
8.
go back to reference Brizel DM, Lin S, Johnson JL et al (1995) The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation. Br J Cancer 72:1120–1124PubMedCentralCrossRefPubMed Brizel DM, Lin S, Johnson JL et al (1995) The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation. Br J Cancer 72:1120–1124PubMedCentralCrossRefPubMed
9.
go back to reference Shi Y, Lee CS, Wu J et al (2005) Effects of hyperbaric oxygen exposure on experimental head and neck tumor growth, oxygenation, and vasculature. Head Neck 27:362–369CrossRefPubMed Shi Y, Lee CS, Wu J et al (2005) Effects of hyperbaric oxygen exposure on experimental head and neck tumor growth, oxygenation, and vasculature. Head Neck 27:362–369CrossRefPubMed
10.
11.
go back to reference Vaupel P, Schlenger K, Knoop C et al (1991) Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res 51:3316–3322PubMed Vaupel P, Schlenger K, Knoop C et al (1991) Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res 51:3316–3322PubMed
12.
go back to reference Thews O, Vaupel P (1996) Relevant parameters for describing the oxygenation status of solid tumors. Strahlenther Onkol 172:239–243PubMed Thews O, Vaupel P (1996) Relevant parameters for describing the oxygenation status of solid tumors. Strahlenther Onkol 172:239–243PubMed
13.
go back to reference Kelleher DK, Matthiensen U, Thews O et al (1996) Blood flow, oxygenation, and bioenergetic status of tumors after erythropoietin treatment in normal and anemic rats. Cancer Res 56:4728–4734PubMed Kelleher DK, Matthiensen U, Thews O et al (1996) Blood flow, oxygenation, and bioenergetic status of tumors after erythropoietin treatment in normal and anemic rats. Cancer Res 56:4728–4734PubMed
14.
go back to reference Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49:6449–6465PubMed Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49:6449–6465PubMed
15.
go back to reference Gray LH, Conger AD, Ebert M et al (1953) The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26:638–648CrossRefPubMed Gray LH, Conger AD, Ebert M et al (1953) The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26:638–648CrossRefPubMed
16.
go back to reference Hall EJ, Giaccia AJ (2011) Radiobiology for the radiologist. Lippincott Williams & Wilkins, Philadelphia Hall EJ, Giaccia AJ (2011) Radiobiology for the radiologist. Lippincott Williams & Wilkins, Philadelphia
17.
go back to reference Hou H, Dong R, Li H et al (2012) Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: a multisite EPR oximetry with implantable resonators. J Magn Reson 214:22–28PubMedCentralCrossRefPubMed Hou H, Dong R, Li H et al (2012) Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: a multisite EPR oximetry with implantable resonators. J Magn Reson 214:22–28PubMedCentralCrossRefPubMed
19.
go back to reference Borges AR, Lopez-Larrubia P, Marques JB et al (2012) MR imaging features of high-grade gliomas in murine models: how they compare with human disease, reflect tumor biology, and play a role in preclinical trials. Am J Neuroradiol 33:24–36CrossRefPubMed Borges AR, Lopez-Larrubia P, Marques JB et al (2012) MR imaging features of high-grade gliomas in murine models: how they compare with human disease, reflect tumor biology, and play a role in preclinical trials. Am J Neuroradiol 33:24–36CrossRefPubMed
20.
go back to reference Matsumoto K, Bernardo M, Subramanian S et al (2006) MR assessment of changes of tumor in response to hyperbaric oxygen treatment. Magn Reson Med 56:240–246CrossRefPubMed Matsumoto K, Bernardo M, Subramanian S et al (2006) MR assessment of changes of tumor in response to hyperbaric oxygen treatment. Magn Reson Med 56:240–246CrossRefPubMed
21.
go back to reference Hallac RR, Zhou H, Pidikiti R et al (2014) Correlations of noninvasive BOLD and TOLD MRI with pO2 and relevance to tumor radiation response. Magn Reson Med 71:1863–1873PubMedCentralCrossRefPubMed Hallac RR, Zhou H, Pidikiti R et al (2014) Correlations of noninvasive BOLD and TOLD MRI with pO2 and relevance to tumor radiation response. Magn Reson Med 71:1863–1873PubMedCentralCrossRefPubMed
22.
go back to reference Ding Y, Mason RP, McColl RW et al (2013) Simultaneous measurement of tissue oxygen level-dependent (TOLD) and blood oxygenation level-dependent (BOLD) effects in abdominal tissue oxygenation level studies. J Magn Reson Imaging 38:1230–1236CrossRefPubMed Ding Y, Mason RP, McColl RW et al (2013) Simultaneous measurement of tissue oxygen level-dependent (TOLD) and blood oxygenation level-dependent (BOLD) effects in abdominal tissue oxygenation level studies. J Magn Reson Imaging 38:1230–1236CrossRefPubMed
23.
go back to reference Bussink J, Kaanders JH, Rijken PF et al (1999) Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xenografts: effects of carbogen and nicotinamide. Radiother Oncol 50:173–184CrossRefPubMed Bussink J, Kaanders JH, Rijken PF et al (1999) Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xenografts: effects of carbogen and nicotinamide. Radiother Oncol 50:173–184CrossRefPubMed
24.
go back to reference Bussink J, Kaanders JH, Rijken PF et al (2000) Changes in blood perfusion and hypoxia after irradiation of a human squamous cell carcinoma xenograft tumor line. Radiat Res 153:398–404CrossRefPubMed Bussink J, Kaanders JH, Rijken PF et al (2000) Changes in blood perfusion and hypoxia after irradiation of a human squamous cell carcinoma xenograft tumor line. Radiat Res 153:398–404CrossRefPubMed
25.
go back to reference Henriques de FB, Zacharatou C, Galland-Girodet S et al (2015) Hypoxia imaging with [18F]-FMISO-PET for guided dose escalation with intensity-modulated radiotherapy in head-and-neck cancers. Strahlenther Onkol 191:217–224CrossRef Henriques de FB, Zacharatou C, Galland-Girodet S et al (2015) Hypoxia imaging with [18F]-FMISO-PET for guided dose escalation with intensity-modulated radiotherapy in head-and-neck cancers. Strahlenther Onkol 191:217–224CrossRef
26.
go back to reference Yaromina A, Thames H, Zhou X et al (2010) Radiobiological hypoxia, histological parameters of tumour microenvironment and local tumour control after fractionated irradiation. Radiother Oncol 96:116–122CrossRefPubMed Yaromina A, Thames H, Zhou X et al (2010) Radiobiological hypoxia, histological parameters of tumour microenvironment and local tumour control after fractionated irradiation. Radiother Oncol 96:116–122CrossRefPubMed
27.
go back to reference Winther M, Alsner J, Tramm T et al (2013) Hypoxia-regulated gene expression and prognosis in loco-regional gastroesophageal cancer. Acta Oncol 52:1327–1335CrossRefPubMed Winther M, Alsner J, Tramm T et al (2013) Hypoxia-regulated gene expression and prognosis in loco-regional gastroesophageal cancer. Acta Oncol 52:1327–1335CrossRefPubMed
28.
go back to reference Brennan DJ, Jirstrom K, Kronblad A et al (2006) CA IX is an independent prognostic marker in premenopausal breast cancer patients with one to three positive lymph nodes and a putative marker of radiation resistance. Clin Cancer Res 12:6421–6431CrossRefPubMed Brennan DJ, Jirstrom K, Kronblad A et al (2006) CA IX is an independent prognostic marker in premenopausal breast cancer patients with one to three positive lymph nodes and a putative marker of radiation resistance. Clin Cancer Res 12:6421–6431CrossRefPubMed
29.
go back to reference Müller A, Remmele S, Wenningmann I et al (2011) Analysing the response in R2* relaxation rate of intracranial tumours to hyperoxic and hypercapnic respiratory challenges: initial results. Eur Radiol 21:786–798CrossRefPubMed Müller A, Remmele S, Wenningmann I et al (2011) Analysing the response in R2* relaxation rate of intracranial tumours to hyperoxic and hypercapnic respiratory challenges: initial results. Eur Radiol 21:786–798CrossRefPubMed
Metadata
Title
Spatial oxygenation profiles in tumors during normo- and hyperbaric hyperoxia
Authors
Prof. Dr. med. Oliver Thews
Prof. Dr. Peter Vaupel
Publication date
01-11-2015
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 11/2015
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-015-0867-6

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