Dependence of FDG uptake on tumor microenvironment.
OBJECTIVE
To investigate the factors affecting the (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in tumors at a microscopic level, by correlating it with tumor hypoxia, cellular proliferation, and blood perfusion.


METHODS
Nude mice bearing Dunning prostate tumors (R3327-AT) were injected with (18)F-FDG and pimonidazole, bromodeoxyuridine, and, 1 min before sacrifice, with Hoechst 33342. Selected tumor sections were imaged by phosphor plate autoradiography, while adjacent sections were used to obtain the images of the spatial distribution of Hoechst 33342, pimonidazole, and bromodeoxyuridine. The images were co-registered and analyzed on a pixel-by-pixel basis.


RESULTS
Statistical analysis of the data obtained from these tumors demonstrated that (18)F-FDG uptake was positively correlated with pimonidazole staining intensity in each data set studied. Correlation of FDG uptake with bromodeoxyuridine staining intensity was always negative. In addition, FDG uptake was always negatively correlated with the staining intensity of Hoechst 33342.


CONCLUSIONS
For the Dunning prostate tumors studied, FDG uptake was always positively correlated with hypoxia and negatively correlated with both cellular proliferation and blood flow. Therefore, for the tumor model studied, higher FDG uptake is indicative of tumor hypoxia, but neither blood flow nor cellular proliferation.
Pugachev
Andrei
A
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. pugachea@mskcc.org
Ruan
Shutian
S
Carlin
Sean
S
Larson
Steven M
SM
Campa
Jose
J
Ling
C Clifton
CC
Humm
John L
JL
D000818:Animals; D001345:Autoradiography; D001562:Benzimidazoles / Q000493:pharmacokinetics; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D015687:Cell Hypoxia; D049109:Cell Proliferation; D004396:Coloring Agents / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
D001562:Benzimidazoles; D004396:Coloring Agents; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C033815:pimonidazole; D001973:Bromodeoxyuridine; D005947:Glucose; C017807:bisbenzimide ethoxide trihydrochloride