Photodynamic therapy involves the use of a non-toxic photosensitizer which exhibits killing effect upon activation by light. It has been used successfully in treating age-related macular degeneration, actinic keratosis and various cancers like lung, bladder and esophageal cancers. The success of photodynamic therapy depends on the properties of the photosensitizer and there is a continuous search for better photosensitizers with desirable photophysical and biochemical effects. In the last few years, we have synthesized a series of silicon(IV) phthalocyanines with different axial substituents and demonstrated their photocytotoxic effects in the in vitro heptocellular carcinoma HepG2 cells. Among them the glucoconjugated silicon(IV) phthalocyanine SiPcGlu is most promising with IC50 value down to nanomolar range in the cell culture system. In the present investigation, the in vivo effect of SiPcGlu was studied in the HepG2 tumor-bearing nude mice model. The biodistribution of SiPcGlu was followed to evaluate its tumor-selectivity and the tumor volume was measured after photodynamic therapy. The level of intrinsic toxicity induced was also investigated by examining the level of plasma enzyme markers. The distribution and clearance results showed that the concentration of SiPcGlu in the tumor was relatively higher at 24 hr post-injection when compared with all the other tissues examined. One percent of initial dose per gram tissue could be found in the tumor while the corresponding values for the other tissues ranged from 0.8% (lung) to 2.5% (skin). Thus, a drug-light interval of 24 hr was selected in the photodynamic therapy experiment. A laser light dose of 30 J/cm2 (bandwidth 675 ± 3 nm) was spotted onto the tumor 24 hr after intravenous injection of the drug (one μmol per kg body weight). Significant tumor regression was observed for the experimental group of mice. Fifteen days after photodynamic treatment, the volume of the tumor was less than 20% of the initial volume while mice in the two control groups, viz. dark control in which the mice received drug but no irradiation and the light control group in which the mice received irradiation but no drug, did not show any tumor regression. The photodynamic treatment did not cause any apparent toxicity to the animals as the plasma levels of the three enzyme markers, alanine transaminase, aspartate transaminase and creatine kinase, were similar in all the three groups of mice. To conclude, the present results suggest that SiPcGlu is a good candidate for further evaluation on its anti-tumor potential. (This project is supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, Project No. CUHK 4569/05M.)

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3569.