Pharmacokinetics of the ¹³C labeled anticancer agent temozolomide detected in vivo by selective cross‐polarization transfer

The anticancer agent temozolomide labeled with ¹³C (8‐Carbamoyl‐3‐13C‐methylimidazo‐[5,1‐d]‐1,2,3,5‐tetrazin‐4‐(3H)‐one), was noninvasively detected in subcutaneous RIF‐1 tumors by a selective cross polarization ¹³C 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 modes of administration (three animals per mode). The half‐life of the drug 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 feasibility of obtaining pharmacokinetics of anticancer agents for individual tumors 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 monitoring the tumor to evaluate drug pharmacokinetics.