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

UNLABELLED

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.

CONCLUSION

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.