Platinum levels in murine tumor following intraperitoneal administration of cisplatin or paraplatin.

Abstract

To design protocols for exploitation of the potential for interaction among the platinum (Pt) chemotherapeutic agents cisplatin and paraplatin and radiation therapy, we measured levels of total platinum in a transplantable murine mammary adenocarcinoma (MTG-B) at different times after ip injection of platinum drugs and in various regimens. Cisplatin (20 mg/kg body weight) or paraplatin (60 or 120 mg/kg body weight) were injected ip in female C3H/HeJ mice bearing MTG-B of about 1 cm diameter. At various times after injection, tumors were removed and processed for acid digestion and total platinum analysis by atomic absorption spectrometry with a graphite furnace. The results of these experiments indicate that intratumoral Pt levels 15 minutes postinjection are higher than at 5 or 30 minutes. At 30 minutes, the Pt concentrations are of the magnitudes of 30 and 50 microM for cisplatin and paraplatin, respectively, that, when added to cells in vitro in combination with radiation therapy, produce the potentiation of cell killing. In addition, for paraplatin, intratumoral Pt levels at 30 minutes following an ip injection are approximately doubled if the tumors receive localized radiotherapy of 20 Gy immediately prior to injection of the drug. This apparent modification of paraplatin pharmacokinetics by radiotherapy might account for some of the supra-additive therapeutic potentiation in MTG-B reported for paraplatin added after irradiation.