High 18F-FDG uptake in microscopic peritoneal tumors requires physiologic hypoxia.
The objective of this study was to examine (18)F-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% O(2) + 5% CO(2)), were intravenously administered (18)F-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 (18)F-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 (18)F-FDG accumulation and were severely hypoxic, with high GLUT-1 expression. Larger tumors (diameter, 1-4 mm) generally had low (18)F-FDG accumulation and were not significantly hypoxic, with low GLUT-1 expression. Carbogen breathing significantly decreased (18)F-FDG accumulation and tumor hypoxia in microscopic tumors but had little effect on GLUT-1 expression.


CONCLUSIONS
There was high (18)F-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 (18)F-FDG uptake.
Li
Xiao-Feng
XF
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. xiao-feng.li@louisville.edu
Ma
Yuanyuan
Y
Sun
Xiaorong
X
Humm
John L
JL
Ling
C Clifton
CC
O'Donoghue
Joseph A
JA
D000388:Air; D000818:Animals; D001345:Autoradiography; D001692:Biological Transport / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051379:Mice; D009593:Nitroimidazoles / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012119:Respiration
D051272:Glucose Transporter Type 1; D009593:Nitroimidazoles; D019788:Fluorodeoxyglucose F18; D002245:Carbon Dioxide; C033815:pimonidazole; C011700:carbogen; D010100:Oxygen