Abstract
Among the primary reasons for failure of anticancer chemotherapy are insufficient drug delivery to the tumor because of inadequate tumor vascularization and/or the antivascular effects of chemotherapy. Thus, determining the spatial intratumoral distribution of anticancer agents by noninvasive methods such as MRI/MRSI is important for monitoring cancer chemotherapy. We therefore studied the distribution of the ^13^C‐labeled anticancer agent temozolomide ([^13^C]TMZ) in MCF‐7 tumor‐bearing mice using ^1^H/^13^C MRSI. In phantom studies inverse ^13^C detection with heteronuclear multiple quantum coherence (HMQC) provided a 2.3‐fold gain in signal‐to‐noise ratio (SNR) over direct nuclear overhauser effect (NOE)‐enhanced ^13^C‐MRS. This enabled detection of [^13^C]TMZ in the micromolar range. Three‐dimensional (3D) maps of drug distribution with a nominal 2.5‐mm isotropic resolution were obtained following intraperitoneal administration of [^13^C]TMZ, for a total dose of 200 mg/kg. The status of the blood supply of tumors was assessed by gadolinium (Gd)‐enhanced dynamic MRI. Nonuniform distributions of the drug and the contrast agent were detected in the tumors. Although carbon‐13 MRSI has an inherently low sensitivity for detection, the novel technique described here demonstrates the feasibility of studying the delivery of ^13^C‐labeled drugs and contrast uptake during the course of chemotherapy. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.