High 18F-FDG uptake in microscopic peritoneal tumors requires physiologic hypoxia Journal Article


Authors: Li, X. F. ; Ma, Y.; Sun, X.; Humm, J. L.; Ling, C. C.; O'Donoghue, J. A.
Article Title: High 18F-FDG uptake in microscopic peritoneal tumors requires physiologic hypoxia
Abstract: The objective of this study was to examine 18F-FDG uptake in microscopic tumors grown intraperitoneally in nude mice and to relate this to physiologic hypoxia and glucose transporter-1 (GLUT-1) expression. Methods: Human colon cancer HT29 and HCT-8 cells were injected intraperitoneally into nude mice to generate disseminated tumors of varying sizes. After overnight fasting, animals, breathing either air or carbogen (95% O2 + 5% CO2), were intravenously administered 18F-FDG together with the hypoxia marker pimonidazole and cellular proliferation marker bromodeoxyuridine 1 h before sacrifice. Hoechst 33342, a perfusion marker, was administered 1 min before sacrifice. After sacrifice, the intratumoral distribution of 18F-FDG was assessed by digital autoradiography of frozen tissue sections. Intratumoral distribution was compared with the distributions of pimonidazole, GLUT-1 expression, bromodeoxyuridine, and Hoechst 33342 as visualized by immunofluorescent microscopy. Results: Small tumors (diameter, <1 mm) had high 18F-FDG accumulation and were severely hypoxic, with high GLUT-1 expression. Larger tumors (diameter, 1-4 mm) generally had low 18F-FDG accumulation and were not significantly hypoxic, with low GLUT-1 expression. Carbogen breathing significantly decreased 18F-FDG accumulation and tumor hypoxia in microscopic tumors but had little effect on GLUT-1 expression. Conclusion: There was high 18F-FDG uptake in microscopic tumors that was spatially associated with physiologic hypoxia and high GLUT-1 expression. This enhanced uptake was abrogated by carbogen breathing, indicating that in the absence of physiologic hypoxia, high GLUT-1 expression, by itself, was insufficient to ensure high 18F-FDG uptake. Copyright © 2010 by the Society of Nuclear Medicine, Inc.
Keywords: controlled study; protein expression; human cell; genetics; disseminated cancer; nonhuman; pathophysiology; cell proliferation; mouse; animal; metabolism; animals; mice; animal tissue; peritoneal neoplasms; tumor volume; oxygen; animal experiment; animal model; drug effect; pathology; hypoxia; gene expression regulation; fluorescent antibody technique; gene expression regulation, neoplastic; cancer cell; fluorodeoxyglucose f 18; fluorodeoxyglucose f18; micrometastasis; pimonidazole; respiration; ascites tumor; cell strain ht29; ht29 cells; anoxia; biological transport; peritoneum tumor; nitroimidazole derivative; autoradiography; nitroimidazoles; glucose transporter 1; glucose transporter type 1; carbogen; carbon dioxide; digital imaging; glucose metabolism; transport at the cellular level; 18f- fluorodeoxyglucose; breathing; air
Journal Title: Journal of Nuclear Medicine
Volume: 51
Issue: 4
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2010-04-01
Start Page: 632
End Page: 638
Language: English
DOI: 10.2967/jnumed.109.071233
PUBMED: 20351353
PROVIDER: scopus
PMCID: PMC2917184
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "CODEN: JNMEA" - "Source: Scopus"
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MSK Authors
  1. Xiao-Feng Li
    11 Li
  2. Xiaorong Sun
    19 Sun
  3. John Laurence Humm
    433 Humm
  4. C Clifton Ling
    331 Ling
  5. Yuanyuan Ma
    18 Ma