Distribution of metal-free sulfonated phthalocyanine in subcutaneously transplanted murine tumors

Metal-free sulfonated phthalocyanine with the average number of sulfonate groups per molecule 2.4 (H2PcS2.4) was recently proved to be an efficient photosensitizer for the photodynamic therapy. Fluorescence spectral imaging microscopy was applied here to study localization and relative concentration of H2PcS2.4 with micron-scale resolution in subcutaneously transplanted murine tumors: Ehrlich mammary gland carcinoma (EC), Lewis lung carcinoma (LLC), P388 lymphoid leukemia (P388) and B16 melanoma (B16). The study of cryogenic tissue sections prepared 24 h after H2PcS2.4 intravenous injection revealed that H2PcS2.4 was present in all tissue structures in the monomeric photoactive state. The preferential accumulation of H2PcS2.4 was documented in tumor cells and adjacent non-tumor tissues (skin structures, fatty tissue, connective tissue enriched in fibrous component and infiltrated with fibroblasts and macrophages) for all the studied tumor models. P388 and B16 were stained with H2PcS2.4 less than adjacent skin structures, whereas EC and LLC accumulated H2PcS2.4 alike or higher than particular skin structures. Staining of EC and LLC was similar and ca. 1.4 and 2 times higher than that of B16 and P388, respectively, thus revealing the differences in ability of particular tumor strains to H2PcS2.4 accumulation. The H2PcS2.4 concentration in remote healthy tissues (skin, muscles and connective tissue) was 2–3 times lower as compared with the analogous tissue structures from the tumor area, whereas subcutaneous fatty tissue staining did not depend on the tissue-totumor distance. The tissue distribution of H2PcS2.4 predefines the combined action of two photodynamic damage mechanisms: eradication of tumor due to the direct tumor cell destruction and suppression of tumor growth due to the injury of growth supporting system.