Enhanced Response of Human Head and Neck Cancer Xenograft Tumors to Cisplatin Combined With 2-Deoxy- d-Glucose Correlates With Increased 18F-FDG Uptake as Determined by PET Imaging

Andrean L Simons; Melissa A Fath; David M Mattson; Brian J Smith; Susan A Walsh; Michael M Graham; Richard D Hichwa; John M Buatti; Ken Dornfeld; Douglas R Spitz

doi:10.1016/j.ijrobp.2007.07.2343

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Enhanced Response of Human Head and Neck Cancer Xenograft Tumors to Cisplatin Combined With 2-Deoxy- d-Glucose Correlates With Increased 18F-FDG Uptake as Determined by PET Imaging

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Enhanced Response of Human Head and Neck Cancer Xenograft Tumors to Cisplatin Combined With 2-Deoxy- d-Glucose Correlates With Increased 18F-FDG Uptake as Determined by PET Imaging

Andrean L Simons, Melissa A Fath, David M Mattson, Brian J Smith, Susan A Walsh, Michael M Graham, Richard D Hichwa, John M Buatti, Ken Dornfeld and Douglas R Spitz

International journal of radiation oncology, biology, physics, Vol.69(4), pp.1222-1230

2007

DOI: 10.1016/j.ijrobp.2007.07.2343

PMCID: PMC2267859

PMID: 17967311

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https://www.ncbi.nlm.nih.gov/pmc/articles/2267859View

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Abstract

To determine whether the response of human head and neck cancer xenografts to cisplatin (CIS) could be enhanced with 2-deoxy- d-glucose (2DG); whether 2-[ 18F]-fluoro-2-deoxy- d-glucose (FDG) uptake correlated with responses to this drug combination; and whether 2DG would enhance CIS-induced radiosensitization. Clonogenic survival responses to CIS + 2DG were determined in FaDu and Cal-27 cells and reduced/oxidized glutathione levels were monitored as parameters indicative of oxidative stress. The efficacy of CIS + 2DG was determined in FaDu and Cal-27 xenografts, and FDG uptake was determined by using positron emission tomography. Use of CIS + 2DG enhanced cell killing of FaDu and Cal-27 cells compared with either drug alone while increasing the percentage of oxidized glutathione in vitro. Use of CIS + 2DG inhibited FaDu and Cal-27 tumor growth and increased disease-free survival compared with either drug alone. The Cal-27 tumors showed greater pretreatment FDG uptake and increased disease-free survival when treated with 2DG + CIS relative to FaDu tumors. Treatment with 2DG enhanced CIS-induced radiosensitization in FaDu tumor cells grown in vitro and in vivo and resulted in apparent cures in 50% of tumors. These results show the enhanced therapeutic efficacy of CIS + 2DG in human head and neck cancer cells in vitro and in vivo compared with either drug alone, as well as the potential for FDG uptake to predict tumor sensitivity to 2DG + CIS. These findings provide a strong rationale for evaluating 2DG + CIS in combined-modality head and neck cancer therapy with radiation in a clinical setting.

Squamous cell carcinoma of the head and neck (HNSCC)

Oxidative stress

2-Deoxy- d-glucose

Cisplatin

Radiation

2-[ 18F]-fluoro-2-deoxy- d-glucose (FDG)–positron emission tomography (PET)

Details

Title: Subtitle: Enhanced Response of Human Head and Neck Cancer Xenograft Tumors to Cisplatin Combined With 2-Deoxy- d-Glucose Correlates With Increased 18F-FDG Uptake as Determined by PET Imaging
Creators: Andrean L Simons - Department of Radiation Oncology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Melissa A Fath - Department of Radiation Oncology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
David M Mattson - Department of Radiation Oncology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Brian J Smith - Department of Biostatistics, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Susan A Walsh - Department of Radiation Oncology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Michael M Graham - Department of Radiology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Richard D Hichwa - Department of Radiology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
John M Buatti - Department of Radiation Oncology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Ken Dornfeld - Department of Radiation Oncology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Douglas R Spitz - Department of Radiation Oncology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Resource Type: Journal article
Publication Details: International journal of radiation oncology, biology, physics, Vol.69(4), pp.1222-1230
DOI: 10.1016/j.ijrobp.2007.07.2343
PMID: 17967311
PMCID: PMC2267859
NLM abbreviation: Int J Radiat Oncol Biol Phys
ISSN: 0360-3016
eISSN: 1879-355X
Publisher: Elsevier Inc
Language: English
Date published: 2007
Academic Unit: Radiology; Oral Pathology, Radiology and Medicine; Research Administration; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Physics and Astronomy; Radiation Oncology; Neurosurgery; Otolaryngology; Holden Comprehensive Cancer Center
Record Identifier: 9983997345902771

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