Photodynamic therapy with intratumoral administration of Lipid-Based mTHPC in a model of breast cancer recurrence.
OBJECTIVE
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.


METHODS
Mice were directly injected into the tumor (IT) with 25 microl 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.


CONCLUSIONS
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.
D'Hallewin
Marie Ange
MA
Centre de Recherche en Automatique de Nancy, Nancy-University, CNRS, Centre Alexis Vautrin, Vandoeuvre les Nancy, France. m.dhallewin@nancy.fnclcc.fr
Kochetkov
Dmitri
D
Viry-Babel
Yan
Y
Leroux
Agnes
A
Werkmeister
Elisabeth
E
Dumas
Dominique
D
Gräfe
Susanna
S
Zorin
Vladimir
V
Guillemin
François
F
Bezdetnaya
Lina
L
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D015552:Injections, Intralesional; D008652:Mesoporphyrins / Q000008:administration & dosage*; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin