PHARMACOKINETICS OF THE C-13 LABELED ANTICANCER AGENT TEMOZOLOMIDE DETECTED IN-VIVO BY SELECTIVE CROSS-POLARIZATION TRANSFER

The anticancer agent temozolomide labeled with C-13 ethylimidazo-[5,1- d]-1,2,3,5-tetrazin-4-(3H)-one), was noninvasively detected in subcuta neous RIF-1 tumors by a selective cross polarization C-13 NMR method, at a field strength of 9.4T., Pharmacokinetics of the drug, at a dose of 150 mg/kg, were determined for intravenous and intraperitoneal mode s of administration (three animals per mode), The half-life of the dru g in the tumors was approximately 60 min. The uptake and clearance of the drug, however, varied significantly between individual hosts, for both modes of administration, These results demonstrate the feasibilit y of obtaining pharmacokinetics of anticancer agents for individual tu mors without the need for a label that might modify drug activity (e.g ., fluorine), The variability of the in vivo measurements, even within the same tumor model, demonstrates the necessity of directly monitori ng the tumor to evaluate drug pharmacokinetics.