Skip to main content
Top
Published in: Radiation Oncology 1/2006

Open Access 01-12-2006 | Research

The influence of tumor oxygenation on 18F-FDG (Fluorine-18 Deoxyglucose) uptake: A mouse study using positron emission tomography (PET)

Authors: Linda W Chan, Sebastien Hapdey, Sean English, Jurgen Seidel, Joann Carson, Anastasia L Sowers, Murali C Krishna, Michael V Green, James B Mitchell, Stephen L Bacharach

Published in: Radiation Oncology | Issue 1/2006

Login to get access

Abstract

Background

This study investigated whether changing a tumor's oxygenation would alter tumor metabolism, and thus uptake of 18F-FDG (fluorine-18 deoxyglucose), a marker for glucose metabolism using positron emission tomography (PET).

Results

Tumor-bearing mice (squamous cell carcinoma) maintained at 37°C were studied while breathing either normal air or carbogen (95% O2, 5% CO2), known to significantly oxygenate tumors. Tumor activity was measured within an automatically determined volume of interest (VOI). Activity was corrected for the arterial input function as estimated from image and blood-derived data. Tumor FDG uptake was initially evaluated for tumor-bearing animals breathing only air (2 animals) or only carbogen (2 animals). Subsequently, 5 animals were studied using two sequential 18F-FDG injections administered to the same tumor-bearing mouse, 60 min apart; the first injection on one gas (air or carbogen) and the second on the other gas. When examining the entire tumor VOI, there was no significant difference of 18F-FDG uptake between mice breathing either air or carbogen (i.e. air/carbogen ratio near unity). However, when only the highest 18F-FDG uptake regions of the tumor were considered (small VOIs), there was a modest (21%), but significant increase in the air/carbogen ratio suggesting that in these potentially most hypoxic regions of the tumor, 18F-FDG uptake and hence glucose metabolism, may be reduced by increasing tumor oxygenation.

Conclusion

Tumor 18F-FDG uptake may be reduced by increases in tumor oxygenation and thus may provide a means to further enhance 18F-FDG functional imaging.
Appendix
Available only for authorised users
Literature
1.
go back to reference Chapman JD, Bradley JD, Eary JF, Haubner R, Larson SM, Michalski JM, Okunieff PG, Strauss HW, Ung YC, Welch MJ: Molecular (functional) imaging for radiotherapy applications: an RTOG symposium. Int J Radiat Oncol Biol Phys 2003, 55: 294-301. 10.1016/S0360-3016(02)04215-3CrossRefPubMed Chapman JD, Bradley JD, Eary JF, Haubner R, Larson SM, Michalski JM, Okunieff PG, Strauss HW, Ung YC, Welch MJ: Molecular (functional) imaging for radiotherapy applications: an RTOG symposium. Int J Radiat Oncol Biol Phys 2003, 55: 294-301. 10.1016/S0360-3016(02)04215-3CrossRefPubMed
3.
go back to reference Teicher BA, Lazo JS, Sartorelli AC: Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res 1981, 41: 73-81.PubMed Teicher BA, Lazo JS, Sartorelli AC: Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res 1981, 41: 73-81.PubMed
4.
go back to reference Moulder JE, Rockwell S: Hypoxic fractions of solid tumors: experimental techniques, methods of analysis, and a survey of existing data. Int J Radiat Oncol Biol Phys 1984, 10: 695-712.CrossRefPubMed Moulder JE, Rockwell S: Hypoxic fractions of solid tumors: experimental techniques, methods of analysis, and a survey of existing data. Int J Radiat Oncol Biol Phys 1984, 10: 695-712.CrossRefPubMed
5.
go back to reference Overgaard J, Horsman MR: Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers. Sem Radiat Oncol 1996, 6: 10-121.CrossRef Overgaard J, Horsman MR: Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers. Sem Radiat Oncol 1996, 6: 10-121.CrossRef
6.
go back to reference Brown JM: Tumor microenvironment and the response to anticancer therapy. Cancer Biol Ther 2002, 1: 453-458.CrossRefPubMed Brown JM: Tumor microenvironment and the response to anticancer therapy. Cancer Biol Ther 2002, 1: 453-458.CrossRefPubMed
7.
go back to reference Khalil AA, Horsman MR, Overgaard J: The importance of determining necrotic fraction when studying the effect of tumour volume on tissue oxygenation. Acta Oncol 1995, 34: 297-300.CrossRefPubMed Khalil AA, Horsman MR, Overgaard J: The importance of determining necrotic fraction when studying the effect of tumour volume on tissue oxygenation. Acta Oncol 1995, 34: 297-300.CrossRefPubMed
8.
go back to reference Krishna MC, English S, Yamada K, Yoo J, Murugesan R, Devasahayam N, Cook JA, Golman K, Ardenkjaer-Larsen JH, Subramanian S, Mitchell JB: Overhauser enhanced magnetic resonance imaging for tumor oximetry: coregistration of tumor anatomy and tissue oxygen concentration. Proc Natl Acad Sci 2002, 99: 2216-2221. 10.1073/pnas.042671399PubMedCentralCrossRefPubMed Krishna MC, English S, Yamada K, Yoo J, Murugesan R, Devasahayam N, Cook JA, Golman K, Ardenkjaer-Larsen JH, Subramanian S, Mitchell JB: Overhauser enhanced magnetic resonance imaging for tumor oximetry: coregistration of tumor anatomy and tissue oxygen concentration. Proc Natl Acad Sci 2002, 99: 2216-2221. 10.1073/pnas.042671399PubMedCentralCrossRefPubMed
9.
go back to reference Halpern HJ, Yu C, Peric M, Barth E, Grdina DJ, Teicher BA: Oxymetry deep in tissues with low-frequency electron paramagnetic resonance. Proc Natl Acad Sci USA 1994, 91: 13047-13051.PubMedCentralCrossRefPubMed Halpern HJ, Yu C, Peric M, Barth E, Grdina DJ, Teicher BA: Oxymetry deep in tissues with low-frequency electron paramagnetic resonance. Proc Natl Acad Sci USA 1994, 91: 13047-13051.PubMedCentralCrossRefPubMed
10.
go back to reference Velan SS, Spencer RG, Zweier JL, Kuppusamy P: Electron paramagnetic resonance oxygen mapping (EPROM): direct visualization of oxygen concentration in tissue. Magn Reson Med 2000, 43: 804-809. 10.1002/1522-2594(200006)43:6<804::AID-MRM5>3.0.CO;2-BCrossRefPubMed Velan SS, Spencer RG, Zweier JL, Kuppusamy P: Electron paramagnetic resonance oxygen mapping (EPROM): direct visualization of oxygen concentration in tissue. Magn Reson Med 2000, 43: 804-809. 10.1002/1522-2594(200006)43:6<804::AID-MRM5>3.0.CO;2-BCrossRefPubMed
11.
go back to reference Warburg OH: The Metabolism of Tumors. London: Constable Publications; 1930. Warburg OH: The Metabolism of Tumors. London: Constable Publications; 1930.
12.
go back to reference Bentzen L, Keiding S, Horsman MR, Gronroos T, Hansen SB, Overgaard J: Assessment of hypoxia in experimental mice tumours by [18F]fluoromisonidazole PET and pO2 electrode measurements. Influence of tumour volume and carbogen breathing. Acta Oncol 2002, 41: 304-312. 10.1080/02841860260088863CrossRefPubMed Bentzen L, Keiding S, Horsman MR, Gronroos T, Hansen SB, Overgaard J: Assessment of hypoxia in experimental mice tumours by [18F]fluoromisonidazole PET and pO2 electrode measurements. Influence of tumour volume and carbogen breathing. Acta Oncol 2002, 41: 304-312. 10.1080/02841860260088863CrossRefPubMed
13.
go back to reference Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P: Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 1996, 56: 4509-4515.PubMed Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P: Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 1996, 56: 4509-4515.PubMed
14.
go back to reference Griffiths JR, Taylor NJ, Howe FA, Saunders MI, Robinson SP, Hoskin PJ, Powell ME, Thoumine M, Caine LA, Baddeley H: The response of human tumors to carbogen breathing, monitored by gradient-recalled echo magnetic resonance imaging. Int J Radiat Oncol Biol Phys 1997, 39: 697-701. 10.1016/S0360-3016(97)00326-XCrossRefPubMed Griffiths JR, Taylor NJ, Howe FA, Saunders MI, Robinson SP, Hoskin PJ, Powell ME, Thoumine M, Caine LA, Baddeley H: The response of human tumors to carbogen breathing, monitored by gradient-recalled echo magnetic resonance imaging. Int J Radiat Oncol Biol Phys 1997, 39: 697-701. 10.1016/S0360-3016(97)00326-XCrossRefPubMed
15.
go back to reference Taylor NJ, Baddeley H, Goodchild KA, Powell ME, Thoumine M, Culver LA, Stirling JJ, Saunders MI, Hoskin PJ, Phillips H, Padhani AR, Griffiths JR: BOLD MRI of human tumor oxygenation during carbogen breathing. J Magn Reson Imaging 2001, 14: 156-163. 10.1002/jmri.1166CrossRefPubMed Taylor NJ, Baddeley H, Goodchild KA, Powell ME, Thoumine M, Culver LA, Stirling JJ, Saunders MI, Hoskin PJ, Phillips H, Padhani AR, Griffiths JR: BOLD MRI of human tumor oxygenation during carbogen breathing. J Magn Reson Imaging 2001, 14: 156-163. 10.1002/jmri.1166CrossRefPubMed
16.
go back to reference Clavo AC, Brown RS, Wahl RL: Fluorodeoxyglucose uptake in human cancer cell lines is increased by hypoxia. J Nucl Med 1995, 36: 1625-1632.PubMed Clavo AC, Brown RS, Wahl RL: Fluorodeoxyglucose uptake in human cancer cell lines is increased by hypoxia. J Nucl Med 1995, 36: 1625-1632.PubMed
17.
go back to reference Clavo AC, Wahl RL: Effects of hypoxia on the uptake of tritiated thymidine, L-leucine, L-methionine and FDG in cultured cancer cells. J Nucl Med 1996, 37: 502-506.PubMed Clavo AC, Wahl RL: Effects of hypoxia on the uptake of tritiated thymidine, L-leucine, L-methionine and FDG in cultured cancer cells. J Nucl Med 1996, 37: 502-506.PubMed
18.
go back to reference Pugachev A, Ruan S, Carlin S, Larson SM, Campa J, Ling CC, Humm JL: Dependence of FDG uptake on tumor microenvironment. Int J Radiat Oncol Biol Phys 2005, 62: 545-553. 10.1016/j.ijrobp.2005.02.009CrossRefPubMed Pugachev A, Ruan S, Carlin S, Larson SM, Campa J, Ling CC, Humm JL: Dependence of FDG uptake on tumor microenvironment. Int J Radiat Oncol Biol Phys 2005, 62: 545-553. 10.1016/j.ijrobp.2005.02.009CrossRefPubMed
19.
go back to reference Kahn BB, Flier JS: Regulation of glucose-transporter gene expression in vitro and in vivo. Diabetes Care 1990, 13: 548-564.CrossRefPubMed Kahn BB, Flier JS: Regulation of glucose-transporter gene expression in vitro and in vivo. Diabetes Care 1990, 13: 548-564.CrossRefPubMed
20.
go back to reference Burgman P, Odonoghue JA, Humm JL, Ling CC: Hypoxia-Induced increase in FDG uptake in MCF7 cells. J Nucl Med 2001, 42: 170-175.PubMed Burgman P, Odonoghue JA, Humm JL, Ling CC: Hypoxia-Induced increase in FDG uptake in MCF7 cells. J Nucl Med 2001, 42: 170-175.PubMed
21.
go back to reference Adam MF, Dorie MJ, Brown JM: Oxygen tension measurements of tumors growing in mice. Int J Radiat Oncol Biol Phys 1999, 45: 171-180. 10.1016/S0360-3016(99)00157-1CrossRefPubMed Adam MF, Dorie MJ, Brown JM: Oxygen tension measurements of tumors growing in mice. Int J Radiat Oncol Biol Phys 1999, 45: 171-180. 10.1016/S0360-3016(99)00157-1CrossRefPubMed
22.
go back to reference Powell ME, Collingridge DR, Saunders MI, Hoskin PJ, Hill SA, Chaplin DJ: Improvement in human tumour oxygenation with carbogen of varying carbon dioxide concentrations. Radiother Oncol 1999, 50: 167-171. 10.1016/S0167-8140(98)00123-6CrossRefPubMed Powell ME, Collingridge DR, Saunders MI, Hoskin PJ, Hill SA, Chaplin DJ: Improvement in human tumour oxygenation with carbogen of varying carbon dioxide concentrations. Radiother Oncol 1999, 50: 167-171. 10.1016/S0167-8140(98)00123-6CrossRefPubMed
23.
go back to reference Aquino-Parsons C, Lim P, Green A, Minchinton AI: Carbogen inhalation in cervical cancer: assessment of oxygenation change. Gynecol Oncol 1999, 74: 259-264. 10.1006/gyno.1999.5443CrossRefPubMed Aquino-Parsons C, Lim P, Green A, Minchinton AI: Carbogen inhalation in cervical cancer: assessment of oxygenation change. Gynecol Oncol 1999, 74: 259-264. 10.1006/gyno.1999.5443CrossRefPubMed
24.
go back to reference Kaanders JH, Bussink J, van der Kogel AJ: ARCON: a novel biology-based approach in radiotherapy. Lancet Oncol 2002, 3: 728-737. 10.1016/S1470-2045(02)00929-4CrossRefPubMed Kaanders JH, Bussink J, van der Kogel AJ: ARCON: a novel biology-based approach in radiotherapy. Lancet Oncol 2002, 3: 728-737. 10.1016/S1470-2045(02)00929-4CrossRefPubMed
25.
go back to reference Bentzen L, Keiding S, Horsman MR, Falborg L, Hansen SB, Overgaard J: Feasibility of detecting hypoxia in experimental mouse tumours with 18F-fluorinated tracers and positron emission tomography – a study evaluating [18F]Fluoro-2-deoxy-D-glucose. Acta Oncol 2000, 39: 629-637. 10.1080/028418600750013320CrossRefPubMed Bentzen L, Keiding S, Horsman MR, Falborg L, Hansen SB, Overgaard J: Feasibility of detecting hypoxia in experimental mouse tumours with 18F-fluorinated tracers and positron emission tomography – a study evaluating [18F]Fluoro-2-deoxy-D-glucose. Acta Oncol 2000, 39: 629-637. 10.1080/028418600750013320CrossRefPubMed
26.
go back to reference Minn H, Clavo AC, Wahl RL: Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging. Nucl Med Biol 1996, 23: 941-946. 10.1016/S0969-8051(96)00134-5CrossRefPubMed Minn H, Clavo AC, Wahl RL: Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging. Nucl Med Biol 1996, 23: 941-946. 10.1016/S0969-8051(96)00134-5CrossRefPubMed
27.
go back to reference Reijnders K, English SJ, Krishna MC, Cook JA, Sowers AL, Mitchell JB, Zhang Y: Influence of body temperature on the BOLD effect in murine SCC tumors. Magn Reson Med 2004, 51: 389-393. 10.1002/mrm.10695CrossRefPubMed Reijnders K, English SJ, Krishna MC, Cook JA, Sowers AL, Mitchell JB, Zhang Y: Influence of body temperature on the BOLD effect in murine SCC tumors. Magn Reson Med 2004, 51: 389-393. 10.1002/mrm.10695CrossRefPubMed
28.
go back to reference Seidel J, Vaquero J, Green MV: Resolution uniformity and sensitivity of the NIH ATLAS small animal PET scanner. Nucl Sci Symp Conf Rec, IEEE 2001, 3: 1555-1558. Seidel J, Vaquero J, Green MV: Resolution uniformity and sensitivity of the NIH ATLAS small animal PET scanner. Nucl Sci Symp Conf Rec, IEEE 2001, 3: 1555-1558.
29.
go back to reference Seidel J, Vaquero J, Pascau J, Desco M, Johnson CA, Green MV: Features of the NIH ATLAS small animal PET scanner and its use with a coaxial small animal volume CT scanner. Biomed Imag Biol 2002, 4: 545-548. Seidel J, Vaquero J, Pascau J, Desco M, Johnson CA, Green MV: Features of the NIH ATLAS small animal PET scanner and its use with a coaxial small animal volume CT scanner. Biomed Imag Biol 2002, 4: 545-548.
30.
go back to reference Seidel J, Vaquero JJ, Green MV: Resolution uniformity and sensitivity of the NIH ATLAS small animal PET scanner: comparison to simulated LSO scanners without depth-of-interaction capability. IEEE Transactions on Nuclear Science 2003, 50: 1347-1350. 10.1109/TNS.2003.817282CrossRef Seidel J, Vaquero JJ, Green MV: Resolution uniformity and sensitivity of the NIH ATLAS small animal PET scanner: comparison to simulated LSO scanners without depth-of-interaction capability. IEEE Transactions on Nuclear Science 2003, 50: 1347-1350. 10.1109/TNS.2003.817282CrossRef
31.
go back to reference Johnson CA, Seidel J, Carson RE, Gandler WR, Sofer A, Green MV, Daube-Witherspoon ME: Evaluation of 3D reconstruction algorithms for a small animal PET camera. IEEE Transactions on Nuclear Science 1997, 44: 1303-1308. 10.1109/23.597005CrossRef Johnson CA, Seidel J, Carson RE, Gandler WR, Sofer A, Green MV, Daube-Witherspoon ME: Evaluation of 3D reconstruction algorithms for a small animal PET camera. IEEE Transactions on Nuclear Science 1997, 44: 1303-1308. 10.1109/23.597005CrossRef
32.
go back to reference Krivitski NM, Starostin D, Smith TL: Extracorporeal recording of mouse hemodynamic parameters by ultrasound velocity dilution. ASAIO J 1999, 45: 3-36. Krivitski NM, Starostin D, Smith TL: Extracorporeal recording of mouse hemodynamic parameters by ultrasound velocity dilution. ASAIO J 1999, 45: 3-36.
33.
go back to reference Watabe H, Channing MA, Riddell C, Jousse F, Libutti SK, Carrasquillo JA, Bacharach SL, Carson RE: Noninvasive estimation of the aorta input function for measurement of tumor blood flow with [O-15]water. IEEE Trans Med Imag 2001, 20: 164-174. 10.1109/42.918468CrossRef Watabe H, Channing MA, Riddell C, Jousse F, Libutti SK, Carrasquillo JA, Bacharach SL, Carson RE: Noninvasive estimation of the aorta input function for measurement of tumor blood flow with [O-15]water. IEEE Trans Med Imag 2001, 20: 164-174. 10.1109/42.918468CrossRef
Metadata
Title
The influence of tumor oxygenation on 18F-FDG (Fluorine-18 Deoxyglucose) uptake: A mouse study using positron emission tomography (PET)
Authors
Linda W Chan
Sebastien Hapdey
Sean English
Jurgen Seidel
Joann Carson
Anastasia L Sowers
Murali C Krishna
Michael V Green
James B Mitchell
Stephen L Bacharach
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2006
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-1-3

Other articles of this Issue 1/2006

Radiation Oncology 1/2006 Go to the issue