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

Magn Reson Med. 1995 Sep;34(3):338-42. doi: 10.1002/mrm.1910340310.

Abstract

The anticancer agent temozolomide labeled with 13C (8-Carbamoyl-3-13C-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4-(3H)-o ne), 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 models 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / pharmacokinetics*
  • Carbon Radioisotopes
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacokinetics
  • Infusions, Intravenous
  • Injections, Intraperitoneal
  • Magnetic Resonance Spectroscopy* / methods
  • Mice
  • Mice, Inbred C3H
  • Neoplasm Transplantation
  • Neoplasms, Experimental / metabolism
  • Temozolomide

Substances

  • Antineoplastic Agents, Alkylating
  • Carbon Radioisotopes
  • Dacarbazine
  • Temozolomide