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Noninvasive 1 H/ 13 C magnetic resonance spectroscopic imaging of the intratumoral distribution of temozolomide
Author(s) -
Kato Yoshinori,
Okollie Baasil,
Artemov Dmitri
Publication year - 2006
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.20831
Subject(s) - temozolomide , nuclear magnetic resonance , magnetic resonance spectroscopic imaging , magnetic resonance imaging , distribution (mathematics) , nuclear medicine , gadolinium , chemistry , imaging phantom , chemotherapy , medicine , radiology , physics , mathematical analysis , mathematics , organic chemistry
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.