Photodynamic therapy with intratumoral administration of lipid-based MTHPC in a model of breast cancer recurrence
Résumé
We have evaluated the use of an intratumoral injection of a liposomal formulation of mTHPC (Foslip®), followed by a red laser light irradiation (l = 652 nm) at different times after injection, in an animal model of local recurrence of breast cancer. The photosensitizer fluorescence assessed by macrofluorescence in excised whole tumors (5 mm) was inhomogeneous and fluorescence intensity increased with time after injection. Model studies in vitro using polarization technique were employed to investigate the transfer of the dye to liposomes, acting as a model for cellular membranes. Maximal mTHPC fluorescence polarization was obtained at 24 hours incubation in an excess of non-loaded liposomes, thus suggesting that at this time point mTHPC has migrated from its lipid based formulation to non-loaded liposomes. This slow rate of mTHPC transfer is consistent with the progressive increase in intratumoral fluorescence intensity. It also correlates with the better PDT efficacy observed at 24 hours after Foslip injection. Minimal damage was observed at skin level. Plasma levels of mTHPC decrease after 15 hours so repeated PDT sessions might be favourable in terms of side effects and tumor response.