Noninvasive 1H/13C magnetic resonance spectroscopic imaging of the intratumoral distribution of temozolomide

Yoshinori Kato, Baasil Okollie, Dmitri Artemov

Research output: Contribution to journalArticlepeer-review

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 13C- labeled anticancer agent temozolomide ([13C]TMZ) in MCF-7 tumor-bearing mice using 1H/13C MRSI. In phantom studies inverse 13C 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 13C-MRS. This enabled detection of [13C]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 [13C]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 MIRSI has an inherently low sensitivity for detection, the novel technique described here demonstrates the feasibility of studying the delivery of 13C-labeled drugs and contrast uptake during the course of chemotherapy.

Original languageEnglish (US)
Pages (from-to)755-761
Number of pages7
JournalMagnetic resonance in medicine
Volume55
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • 3D imaging
  • HMQC
  • Indirect H/C MRS
  • Intratumoral distribution
  • Magnetic resonance spectroscopic imaging (MRSI)
  • Temozolomide

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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