Speakers

Carole D. Thomas

  • Designation: Researcher, Institut Curie
  • Country: France
  • Title: Enhanced Efficacy of PDT (PhotoDynamic Therapy) when Combined with Nitroglycerin Ointment Administration on Xenografted Retinoblastoma in Mice

Biography

Dr. Carole D. Thomas is a researcher who works on cancer. Her experience in the Institut Gustave Roussy provided her with strong competencies in radiotherapy and also in radio-pathology of solid tumors in xenograft tumors and in patients too. The integration of the Institut Curie since 1999 permitted her to develop knowledge of MRI and more precisely MRI sodium imaging which is a novel and completely non-invasive imaging technique for tumor detection and treatment assessment. For several years, Dr Thomas has been working on photodynamic therapy applied to different types of cancers and in particular to ocular tumors like retinoblastoma.

Abstract

PDT uses a non-mutagen photosensitizing agent (PS: glycoconjugated porphyrin derivative) activated by red light exposure. Absorption of light initiates photochemical reactions leading to the generation of cytotoxic photoproducts (ROSs: oxygen reactive species) responsible for the therapeutic effects [1]. We propose to increase the PDT efficiency (on our least responsive retinoblastoma line to treatment) with a better PS delivery in the tumor generated by NG which is known to dilate vessels and enhance the permeability and retention of macromolecules in solid tumors [2].

Methods: In vivo follow-up of the therapeutic effects was performed by sodium MRI which directly monitors variations of sodium concentrations in a non-invasive way and can be used to follow up the tumor response to therapy [3]. NG ointment was applied one hour before PDT. The PDT protocol implied a double tumor targeting, cellular and vascular. A first PS dose was injected followed by a second one, separated by a 3 h interval. The time-lapse allowed the PS molecules to penetrate tumor cells. Ten minutes after the second dose, the PS was red light activated.

Results: The PDT efficacy (increase of necrosis, decrease of the tumor volume) was enhanced by applying NG ointment on the skin of tumor-bearing animals.

Conclusion: NG increases the PDT efficacy by enhancing the intratumor concentration of PS inducing a more significant production of ROSs on the illuminated region increasing thus the propagation of cellular death signaling deeper into the tumor (bystander effect).

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