In vivo pharmacokinetics and photodynamic effect of Foscan®
(mTHPC) in tumor tissue of mice bearing human colon adenocarcinoma
H. Rezzoug a, O. A'Amar a,b,
L. Bezdetnaya * a,c and F.Guillemin a,b
a Centre Alexis Vautrin, Unité de Recherche en Thérapie Photodynamique,
URA CNRS D0821, 54511 Vandoeuvre-lès-Nancy Cedex, France
b Centre de Recherche en Automatique de Nancy CRAN URA CNRS DO821
c Russian State Medical University
Key words : Photodynamic therapy, Foscan¨ (mTHPC), Spectrofluorometry,
cytotoxicity, nude mice, human colon adenocarcinoma.
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Foscan® or meta-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics was
investigated using non invasive light induced mTHPC fluorescence emission analysis.
Tumor/healthy tissue mTHPC fluorescence ratios were analyzed to determine the optimal time
for photodynamic therapy (PDT) after injection in nude mice xenografted with HT29 human
colon adenocarcinoma cells. After recording autofluorescence spectra in tumor and normal
surrounding tissues, the mice were injected intraperitoneally with mTHPC (0.3 mg/kg b.w).
In vivo fluorescence emission spectra normalized to the autofluorescence spectrum
were recorded at different time (4 h - 10 days). The maximum fluorescence ratio
(tumor/healthy tissue) of mTHPC (652 nm) was reached 72 h after injection.
Pharmacodynamic activity of mTHPC was then evaluated in HT29 tumor bearing mice injected
intraperitoneally (0.3 mg/kg b.w) and irradiated 72 hours after injection at 650 nm, 10
J/cm2 using a dye laser. Two fluences rates were tested : 32 mW/cm2;
and 160 mW/cm2. Responses were evaluated from tumor volume measurement. Tumor
volume was measured every 2 day and normalized to the initial volume. A continuous growth
was observed in the control groups (neither drug nor light, or drug only or light only).
Tumors exposed to 160 mW/cm2 showed a growth delay (d2-d4). Regression was
observed in tumors treated at 32 mW/cm2 between d2-and d6. Seventy-two hours
time interval between injection and light exposure seems appropriate for mTHPC-PDT. In
addition, this study confirms that under our experimental conditions the fluence rate is
of major importance in mTHPC PDT, lower fluence rate yielding higher therapeutic effect.