In vivo monitoring of the death rate of artificial murine pulmonary micrometastases.

A system is described for direct monitoring of the death rate of artificial murine pulmonary microscopic metastases in vivo. Metastatic fibrosarcoma cells or benign connective tissue cells labeled with [125I]iododeoxyuridine were injected i.v. Comparison of the long-term radioactive decay rate of these two cell types in the lung permitted identification of the portion of the decay curve reflecting the initial period of micrometastasis development and growth. About 5% of the injected tumor cells were retained in the lung in micrometastasis, and their average death rate could be monitored by loss of radioactivity from the lung. Systemic methotrexate (75.0 mg/kg) was administered as a single dose 80 hr after injection of tumor cells at a time when micrometastases had not yet become vascularized. This treatment killed about 60% of the micrometases and suppressed the appearance of gross metastases at 14 days.