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Evaluation of ( E )‐2′‐deoxy‐2′‐(fluoromethylene)cytidine on the 9L rat brain tumor model using MRI
Author(s) -
Ross Brian D.,
Chenevert Thomas L.,
Garwood Michael,
Kim Boklye,
Stegman Lauren D.,
BenYoseph Oded,
Zwolshen John,
Rehemtulla Alnawaz,
Sunkara Prasad S.
Publication year - 2003
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.813
Subject(s) - in vivo , brain tumor , cytidine , cancer research , in vitro , magnetic resonance imaging , medicine , metabolite , glioma , pathology , nuclear medicine , chemistry , biology , biochemistry , enzyme , radiology , microbiology and biotechnology
( E )‐2′‐deoxy‐2′‐(fluoromethylene)cytidine (FMdC), was evaluated as a potential treatment for malignant gliomas using the rat 9L brain tumor model. FMdC was shown to be an effective inhibitor of cell proliferation in cultured 9L cells with an EC 50 of 40 ng/ml. In vitro studies also revealed that this compound significantly inhibited incorporation of [ 3 H]thymidine in 9L cells. In vivo therapeutic efficacy of FMdC was evaluated in rats harboring intracerebral 9L tumors which were treated daily with 15 mg/kg, i.p. Treatment response was quantified from changes in tumor growth rates as assessed from sequential magnetic resonance imaging (MRI) tumor volume measurements. In vivo tumor cell kill in individual animals was calculated by fitting tumor volume data with an iterative computer routine. It was estimated that therapeutically responsive rats treated with FMdC daily produced a ≥ 0.1 log kill per therapeutic dose which resulted in a significant reduction in tumor growth rate. In addition, localized 1 H‐MRS of intracerebral 9L tumors revealed changes in metabolite levels which correlated with therapeutic response. These results provide evidence supporting the use of FMdC in clinical trials for the treatment of malignant gliomas and reveals that MR can play an important role in the pre‐clinical evaluation of novel compounds using orthotopic tumor models. Copyright © 2003 John Wiley & Sons, Ltd.