Selective retention of rhodamine-123 by malignant glioma in the rat

Levels of rhodamine 123 (Rh-123), a new antineoplastic drug, were measured using high performance liquid chromatography in normal brain, malignant glioma and brain adjacent to tumor after a single intravenous injection of drug into rats with intracerebral tumors. Consistently higher levels of Rh-123 were seen in tumor compared to normal brain at all times. Tumor levels of Rh-123 increased up to a maximum level of 9.35 nm/mg at 5 hours after intravenous injection (10 mg/kg), after which Rh-123 levels slowly decreased. Rh-123 concentration in serum reached a maximum level immediately after intravenous injection and Rh-123 was eliminated from the serum according to first order kinetics. The delayed (5 hours after injection) increase in tumor concentration of Rh-123 may reflect tumor hypoperfusion and/or the time required for the compound to diffuse from the blood to the cells within the tumor due to the blood brain barrier. These findings have directed us to study low dose continuous infusion and direct intratumoral injection of Rh-123 as ways of achieving higher Rh-123 levels in tumor with less risk of systemic toxicity due to elevated serum Rh-123 levels.