title: Noninvasive 1H/13C magnetic resonance spectroscopic imaging of the intratumoral distribution of temozolomide.
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 MRSI 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.
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kato
authors.forename: Baasil
authors.initials: B
authors.lastname: Okollie
authors.forename: Dmitri
authors.initials: D
authors.lastname: Artemov
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000378:metabolism*; D002247:Carbon Isotopes; D003287:Contrast Media / Q000493:pharmacokinetics*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D021621:Imaging, Three-Dimensional; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D019047:Phantoms, Imaging; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002247:Carbon Isotopes; D003287:Contrast Media; D003606:Dacarbazine; D019786:Gadolinium DTPA; D000077204:Temozolomide