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- W2072811230 abstract "A glucuro-conjugated carbamate derivative of 5-fluorouracil (5-FU), originally designed as a prodrug for antibody-directed enzyme prodrug therapy (ADEPT) application, has been used for direct in vivo observation of in situ 5-FU generation in two human colon tumors heterotransplanted in nude mice. Because of the very fast elimination of glucuro-conjugated drugs, this observation required intratumoral injection. These tumors, when becoming necrotic, are rich enough in β-glucuronidase to allow 19F magnetic resonance spectroscopy monitoring, at the tumor level, of both prodrug elimination and 5-FU liberation without preliminary treatment by a specifically targeted enzyme conjugate. Convenient tumors have been selected by magnetic resonance imaging (MRI) on the basis of a correlative study between MRI and conventional histology. This contribution is the first report evidencing such a direct intra-tumoral conversion of a glucuro-conjugated prodrug into the expected active drug. This method, which should allow overall estimation of the β-glucuronidase content of tumors, might also be helpful for selecting tumors as specific targets for non-toxic glucuro-conjugated prodrugs without prior treatment with a fusion protein. Copyright © 2000 John Wiley & Sons, Ltd. Abbreviations used: ADEPT antibody-directed enzyme prodrug therapy FID fast induction decay; 5-FU 5-fluorouracil; MRI magnetic resonance imaging; MRS magnetic resonance spectroscopy; NMR nuclear magnetic resonance; ppm, parts per million." @default.
- W2072811230 created "2016-06-24" @default.
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- W2072811230 date "2000-01-01" @default.
- W2072811230 modified "2023-09-25" @default.
- W2072811230 title "Directin vivo observation of 5-fluorouracil release from a prodrug in human tumors heterotransplanted in nude mice: a magnetic resonance study" @default.
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- W2072811230 doi "https://doi.org/10.1002/1099-1492(200008)13:5<306::aid-nbm639>3.0.co;2-p" @default.
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