Biodistribution of 14C-misonidazole as a probe for hypoxic cells in a murine tumor model.

BACKGROUND

To evaluate potential of misonidazole (MISO) as a probe for hypoxia, the biodistribution of 14C-MISO was investigated in a murine tumor model.

MATERIALS AND METHODS

Following intraperitoneal injection of 14C-MISO in C57BL/6 mice with implanted meningial sarcoma tumors in the thighs, the animals were sacrificed at various times (0.5-120 hours), and 14C labeling was measured by a liquid-scintillation counter. The necrotic zone of tumor was identified by its appearance and separated from the non-necrotic tissue.

RESULTS

Concentration-time curves revealed a higher 14C label in the hypoxic areas, and the difference in 14C label between hypoxic and oxic areas widened as time elapsed.

CONCLUSIONS

These results suggest that MISO bound the hypoxic cells more firmly, and the difference in 14C label reflects differences in the bioreductive ability of MISO in these cells. These promising results indicate the feasibility of MISO analogues as a non-invasive probe for hypoxic cell identification.