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Communication Dans Un Congrès Année : 2008

Response surface methodology: an experimental approach to optimize in vivo modalities of photodynamic therapy

Résumé

Purpose: Photodynamic Therapy (PDT) is based on the interaction of a photosensitizing agent (PS), light and oxygen, and a major difficulty is to select adequate treatment conditions. Response surface methodology (RSM), a black-box modeling approach based on a specific design of experiments, was used to optimize in vivo PDT conditions with a new peptide-conjugated PS targeting neuropilin-1. Methods and Materials: a Doehlert experimental design was implemented to infer a response surface model of the growth of U87 tumors xenografted in nude mice treated by PDT with a fixed drug-light interval of 4h. The Doehlert design allows the experimenter to divide by eight the number of experiments in comparison with a classical full factorial design. A new tumor growth statistics, entitled intrinsic diameter growth rate, was preferred to the tumor growth delay and the relative tumor volumes as response variable (variable to explain by the model). The three considered factors (explanatory variables) were the fluence rate, the fluence and the PS dose. The coefficients of the response surface model were obtained by a multiple linear regression method implemented into the Nemrod-W® software. Results: the multivariate and nonlinear relationships between the PDT outcome and the three examined factors were determined. The estimated coefficients of the response surface model provided quantitative information about the effects and interactions of factors on the response variable. With only 13 experimental conditions tested (each one carried out on 5 mice), an optimal PDT condition was selected (PS dose: 2.80 mg/kg; fluence: 120 J/cm2; fluence rate: 95 mW/cm2). With this condition, PDT efficacy using the peptide-conjugated PS was compared to PDT with the non-conjugated PS, and we showed that tumor growth was significantly delayed (Kaplan-Meier: p=0.0054). Conclusions: The intrinsic diameter growth rate, presented herein as a new characteristic of the tumor growth, is complementary to the tumor growth delay and has the main advantage in comparison with the traditional statistics to be independent from the initial volume of the tumor. Secondly, from a methodological point of view, RSM appears as a useful experimental approach for rapid testing of different treatment conditions, and the determination of optimal values of PDT factors for any PS.

Domaines

Cancer
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Dates et versions

hal-00338304 , version 1 (12-11-2008)

Identifiants

  • HAL Id : hal-00338304 , version 1

Citer

Loraine Tirand, Thierry Bastogne, Denise Bechet, Michel Linder, Noémie Thomas, et al.. Response surface methodology: an experimental approach to optimize in vivo modalities of photodynamic therapy. Photodynamic Therapy and Photodiagnosis in Clinical Practice, PDT 2008, Oct 2008, Brixen, Italy. pp.Poster session B-01. ⟨hal-00338304⟩
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