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Photodynamic therapy with intratumoral administration of Lipid‐Based mTHPC in a model of breast cancer recurrence
Author(s) -
D'Hallewin Marie Ange,
Kochetkov Dmitri,
ViryBabel Yan,
Leroux Agnes,
Werkmeister Elisabeth,
Dumas Dominique,
Gräfe Susanna,
Zorin Vladimir,
Guillemin François,
Bezdetnaya Lina
Publication year - 2008
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.20662
Subject(s) - liposome , photodynamic therapy , fluorescence , chemistry , photosensitizer , fluorescence anisotropy , biophysics , medicine , membrane , photochemistry , biochemistry , biology , optics , physics , organic chemistry
Background and Objectives Generalized skin sensitization is a main drawback of photodynamic therapy with systemic administration of photosensitizers. We have evaluated the potential use of an intratumoral injection of a liposomal formulation of mTHPC (Foslip) in a mouse model of local recurrence of breast cancer. Materials and Methods Mice were directly injected into the tumor (IT) with 25 µl of a Foslip suspension (0.15 mg/ml) and illumination (652 nm, 20 J/cm 2 ) was performed at different time points with pathological assessment after 48 hours. In a parallel mice series plasma samples were obtained at different endpoints after IT Foslip injection for HPLC analysis and the tumors were subjected in toto to macrofluorescence imaging. Fluorescence polarization measurements were conducted in vitro to estimate the rate of sensitizer redistribution from liposomes. Results Optimal, albeit partial, cure rates were obtained at 24 hours post‐sensitizer and uninistration. Inhomogeneous and weak fluorescence was observed at early time points and became maximal at 24 hours. Plasma levels of mTHPC increased until 15 hours. Fluorescence polarization measurements showed a slow sensitizer transfer from liposomes to model membranes. Discussion and Conclusion The weak intratumoral fluorescence at early time points could be explained by concentration quenching within the liposomes as evidenced from fluorescence polarization studies. Progressive mTHPC redistribution from liposomes and its further incorporation into tumor tissue resulted in fluorescence build‐up over time with a maximum at 24 hours post‐injection. This correlates perfectly with the best therapeutic effect at this time point. The absence of total cure can be attributed to inhomogeneous photosensitizer distribution. mTHPC is reabsorbed into the blood stream but the total administered amount is much reduced as opposed to systemic administration so that repeated PDT sessions might be favorable in terms of side effects and tumor response. Lesers Surg. Med. 40:543–549, 2008. © 2008 Wiley‐Liss, Inc.