Photosensitization by the near-IR-absorbing photosensitizer lutetium texaphyrin: Spectroscopic, in vitro and in vivo studies

The spectroscopic and biological properties of the new photosensitizer lutetium texaphyrin (Lu-Tex) were assessed in vitro and in vivo on a C26 colon carcinoma model, in comparison with hematoporphyrin (Hp), photofrin II (PII) and chlorin 65 (Ch1). Strong binding of Lu-Tex to lipid bilayer membranes was observed. The results of confocal fluorescence microscopy on C26 cells showed that Lu-Tex was localized in small vesicles in the cytoplasm, possibly in the lysosomes, while ChI and Hp were distributed in larger cytoplasmic vesicles attributed to mitochondria. Scanning electron microscopy and X-ray microanalysis revealed that photodynamic therapy with Lu-Tex induced only slight damage to the cell membrane, leading to a delayed cell response. Ch1 and Hp caused significant structural damage to the outer cell membrane, resulting in ionic imbalance and fast cell death. The in vitro quantitative assessment of the relative efficiency per absorbed photon of the sensitizers revealed that Lu-Tex was less effective than ChI and Hp. However, the results of our in vivo study showed that at the same light and drug doses the anti-tumor efficiency of the agents was in the following order: Lu-Tex > Ch1 > PII. The strong in vivo anti-tumor effect of Lu-Tex can be explained by its higher integrated absorption in the long-wavelength range.