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Investigational New Drugs
Published in: Investigational New Drugs 1/2011

01-02-2011 | PRECLINICAL STUDIES

Preclinical activity of F14512, designed to target tumors expressing an active polyamine transport system

Authors: Anna Kruczynski, Isabelle Vandenberghe, Arnaud Pillon, Sabrina Pesnel, Liliane Goetsch, Jean-Marc Barret, Yves Guminski, Alain Le Pape, Thierry Imbert, Christian Bailly, Nicolas Guilbaud

Published in: Investigational New Drugs | Issue 1/2011

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Summary

We have exploited the polyamine transport system (PTS) to deliver selectively a spermine-drug conjugate, F14512 to cancer cells. This study was aimed to define F14512 anticancer efficacy against tumor models and to investigate whether fluorophor-labeled polyamine probes could be used to identify tumors expressing a highly active PTS and that might be sensitive to F14512 treatments. Eighteen tumor models were used to assess F14512 antitumor activity. Cellular uptake of spermine-based fluorescent probes was measured by flow cytometry in cells sampled from tumor xenografts by needle biopsy. The accumulation of the fluorescent probe within B16 tumors in vivo was assessed using infrared fluorescence imaging. This study has provided evidence of a major antitumor activity for F14512. Significant responses were obtained in 67% of the tumor models evaluated, with a high level of activity recorded in 33% of the responsive models. Complete tumor regressions were observed after i.v., i.p. or oral administrations of F14512 and its antitumor activity was demonstrated over a range of 2–5 dose levels, providing evidence of its good tolerance. The level of cellular fluorescence emitted by the fluorescent probes was higher in cells sampled from tumors sensitive to F14512 treatments than from F14512-refractory tumors. We suggest that these probes could be used to identify tumors expressing a highly active PTS and guide the selection of patients that might be treated with F14512. These results emphasize the preclinical interest of this novel molecule and support its further clinical development.
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Metadata
Title
Preclinical activity of F14512, designed to target tumors expressing an active polyamine transport system
Authors
Anna Kruczynski
Isabelle Vandenberghe
Arnaud Pillon
Sabrina Pesnel
Liliane Goetsch
Jean-Marc Barret
Yves Guminski
Alain Le Pape
Thierry Imbert
Christian Bailly
Nicolas Guilbaud
Publication date
01-02-2011
Publisher
Springer US
Published in
Investigational New Drugs / Issue 1/2011
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-009-9328-3

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