Tumor Localization and Photosensitization by Sulfonated Derivatives of Tetraphenylporphine

We have examined transport, sites of photosensitization, and plasma protein binding by sulfonated derivatives of tetraphenylporphine in vitro and tumor localization of these products in vivo. Studies carried out in culture indicate that the mono‐sulfonated porphyrin sensitized mainly at intracellular loci while drugs with 2 or 3 sulfonates caused photodamage at membrane sites. But the number and distribution of sulfonates were majors factor in both accumulation and efficiency of photodamage. The product with 2 adjacent sulfonates was the most potent photosensitizer; the presence of more or fewer sulfonate residues led to reduced uptake and sensitization. Steady‐state accumulation of drugs with one, two (opposite), three or four sulfonates was rapid, while uptake of the disulfonated (on adjacent rings) porphine was slower. Products bearing one to four sulfonates localized equally well in vivo, but sites of localization varied considerably. Drugs with one sulfonate, or two sulfonates on adjacent rings partitioned into neoplastic cells, analogs with two (opposite), three or four sulfonates partitioned to tumor stroma. Plasma binding studies show that drugs with one or two (adjacent) sulfonates bound to VLDL, LDL and HDL components of plasma, while the tri and tetra‐sulfonated analogs bound progressively more to albumin. These results suggest that tumor localization can occur via two pathways: one mediated by lipoprotein binding and leading to dye accumulation in neoplastic cells, another associated with albumin binding and leading to dye accumulation in stromal elements of neoplastic tissues.