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Tumor Selectivity at Short Times Following Systemic Administration of a Liposomal Temoporfin Formulation in a Murine Tumor Model
Author(s) -
Svensson Jenny,
Johansson Ann,
Gräfe Susanna,
Gitter Burkhard,
Trebst Tilmann,
Bendsoe Niels,
AnderssonEngels Stefan,
Svanberg Katarina
Publication year - 2007
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2007.00146.x
Subject(s) - photosensitizer , biodistribution , chemistry , photodynamic therapy , chlorin , liposome , selectivity , pharmacology , biophysics , chromatography , biochemistry , medicine , in vitro , photochemistry , biology , organic chemistry , catalysis
Meso‐tetra(hydroxyphenyl)chlorin (mTHPC) (INN: Temoporfin) is one of the most potent photodynamically active substances in clinical use. Treatment protocols for Temoporfin‐mediated photodynamic therapy often rely on drug‐light intervals of several days in order for the photosensitizer to accumulate within the target tissue, though tumor selectivity is limited. Here, the mTHPC localization was studied at 2–8 h following systemic administration of a liposomal Temoporfin formulation (0.15 mg kg −1 b.w.) in HT29 human colon adenocarcinoma in NMRI nu/nu mice. Photosensitizer distribution within tumor and internal organs was investigated by means of high performance liquid chromatography following chemical extraction, as well as in situ fluorescence imaging and point‐monitoring fluorescence spectroscopy. For tumor tissue, the Temoporfin concentrations at 4 h (0.16 ± 0.024 ng mg −1 ) and 8 h (0.18 ± 0.064 ng mg −1 ) were significantly higher than at 2 h (0.08 ± 0.026 ng mg −1 ). The average tumor‐to‐muscle and the tumor‐to‐skin selectivity were 6.6 and 2, respectively, and did not vary significantly with time after photosensitizer injection. In plasma, the Temoporfin concentration was low (0.07 ± 0.07 ng mg −1 ) and showed no significant variation with time. Our results indicate a rapid biodistribution and clearance from the bloodstream. Within the same type of organ, data from both fluorescence methods generally exhibited a significant correlation with the extraction results.