Distribution of 3-amino-1-hydroxypropane-1,1-diphosphonic acid in rats and effects on rat osteosarcoma

The distribution of 14C-APD and 99mTc-APD (APD = 3-amino-1-hydroxypropane-1,1-diphosphonic acid) in untreated rats and in rats bearing intratibially transplanted osteosarcomas was investigated autoradiographically and scintigraphically. Also investigated was the effect of high doses of APD on survival time and tumor growth of osteosarcoma-bearing rats. Intravenous administration of APD resulted in high rates of APD accumulation in bones, tumor tissue and pulmonary metastases as well as in dose-related accumulation in the liver. No significant increase in the median survival time of tumor-bearing animals was achieved at the two dosage schemes tested, i.e. 2 X 23.5 mg/kg and 10 X 11.75 mg/kg APD. The growth of primary tumors was slightly increased by administration of APD. The chemosensitivity of the transplantable osteosarcoma model was demonstrated by comparison with dacarbazine-treated control animals.