Noninvasive spatially resolved kinetic study of hydrolyzable camptothecin antitumor drugs in vitro and in vivo by confocal scanning microspectrofluorometry

Igor Chourpa; Serguei Charonov; Alexandre Kokota; Jean-Francois Riou; Michel Manfait

doi:10.1117/12.307339

10 April 1998 Noninvasive spatially resolved kinetic study of hydrolyzable camptothecin antitumor drugs in vitro and in vivo by confocal scanning microspectrofluorometry

Igor Chourpa, Serguei Charonov, Alexandre Kokota, Jean-Francois Riou, Michel Manfait

Author Affiliations +

Proceedings Volume 3259, Systems and Technologies for Clinical Diagnostics and Drug Discovery; (1998) https://doi.org/10.1117/12.307339
Event: BiOS '98 International Biomedical Optics Symposium, 1998, San Jose, CA, United States

Abstract

Hydrolysis of the lactone ring of camptothecins (CPTs) leads to a loss of their antitumor activity. The non-hydrolyzable derivatives are also inactive. Thus, the state of the lactone ring during the drug interaction with biological partners is of a great interest. High performance liquid chromatography currently employed to study the lactone hydrolysis in free CPTs can not be applied to the drug- target complexes and in vivo measurements. We followed kinetics of the lactone hydrolysis in CPTs using hydrolysis- induced time-dependent evolution of their fluorescence spectra. Spectra were obtained from micro-volumes of the samples under the microscope of a computer-controlled confocal microspectrofluorometer (M51, DILOR, France). Spectral recording and treatment (filtering, decomposition into model spectra of the intact and hydrolyzed forms, etc.) were performed using a software package developed in our laboratory. Data obtained for a series of CPTs at very low concentrations, ca. 10^-7 M, demonstrated a good reproducibility, even at basic pH, where the hydrolysis is fast. Then the kinetics studies were extended to CPTs in complexes with their potential biological targets, DNA and topoisomerase I, in vitro. The in vivo studies of the lactone status at the level of single living cancer cells treated with CPTs are actually in progress.

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Igor Chourpa, Serguei Charonov, Alexandre Kokota, Jean-Francois Riou, and Michel Manfait "Noninvasive spatially resolved kinetic study of hydrolyzable camptothecin antitumor drugs in vitro and in vivo by confocal scanning microspectrofluorometry", Proc. SPIE 3259, Systems and Technologies for Clinical Diagnostics and Drug Discovery, (10 April 1998); https://doi.org/10.1117/12.307339

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