VALIDITY AND USEFULNESS OF HUMAN TUMOR-MODELS ESTABLISHED BY INTRATIBIAL CELL INOCULATION IN NUDE RATS

Intratibial injection in nude rats of 1 x 10(6) OHS, MHMX, and LOX hum an tumor cells resulted in each case in progressively growing bone tum ors. When the diameter of the affected leg had increased by 2-3 mm, th e animals were examined for uptake of Tc-99m-methylenediphosphonate. T he OHS osteosarcoma tumors caused sclerotic lesions with high and unif orm isotope uptake, and the MHMX unclassified sarcoma showed a mixed p attern with both sclerotic and lytic areas, whereas the LOX melanoma c aused lytic bone lesions with low uptake of the radionuclide. These fi ndings were compared with the results of analogous investigations prev iously performed in the patients from whom the tumor lines originated. Striking similarities in both the morphology and the scintigraphic im ages were observed between corresponding tumors in rats and humans, wi th results supporting the clinical relevance of the model systems. Whe n the LOX model was used for therapy experiments, doxorubicin had no e ffect on the growth of the tibial tumors, which in the control group a ppeared after a latency of 13.5 days. The alkylating agent mitozolomid e increased the median tumor-free latency to 47 days in 7 rats, and 5 animals did not develop tumors within the observation period of 60 day s. Doxorubicin was ineffective also against the OHS tumor, whereas ifo sfamide and the radionuclide Sr-89-chloride showed significant antitum or activity. The disease-free latency increased from 20 days, in the c ontrol animals, to 45 and 28.5 days, respectively, in the 2 treated gr oups, in which 2 of 7 and 2 of 10 rats were without tumors at 60 days. The data demonstrate that the tibial models discriminated between the action of the different therapeutic agents, and suggest that they may be useful in selecting compounds with clinical activity against skele tal tumors.