aluminum-tetrasulfophthalocyanine and Colonic-Neoplasms

Photodynamic therapy (PDT) involves the use of photosensitizing drugs combined with light to treat tumors. Laser systems, the current source of light for PDT, have several inherent drawbacks: the spectrum is essentially monochromatic which may be problematic for second generation photosensitizers, the systems are bulky and nearly impossible to move between hospital locations and require complicated electrical and cooling installations, the cost of a typical system is enormous, and its maintenance and operation require highly trained personnel. We now introduce a new non-laser light system, Versa-Light, which appears to work as effectively and has none of the above drawbacks.. A series of in vitro studies were performed using various murine and human normal and cancer cells which underwent PDT using aluminum phthalocyanine (AlPcS4) as a photosensitizer and Versa-Light as the light source.. PDT of cancer cells at light energy levels of 50, 100 and 200 j/cm2 significantly decreased cell viability. PDT also decreased cell viability of normal murine splenocytes and normal human lymphocytes, but to a lesser extent. The observed significant hyperthermia was light dose-dependent.. We believe that Versa-Light can replace laser systems as an enhanced light source for PDT. Further in vitro and pre-clinical studies are in progress.

Topics: Animals; Colonic Neoplasms; Female; Fiber Optic Technology; Humans; In Vitro Techniques; Indoles; K562 Cells; Light; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Tumor Cells, Cultured; Xenon

Immunophototherapy of cancer combines the specificity of a monoclonal antibody (MAb) to an overexpressed tumor marker with the phototoxic properties of a conjugated dye. Aluminum tetrasulfophthalocyanine (AlPcS4) was covalently coupled to a 35A7 MAb directed against carcinoembryonic antigen (CEA) via a five-carbon spacer chain (A1) to yield conjugates with a molar ratio ranging from 5 to 16 mol of AlPcS4 per mol of 35A7 MAb. Conjugates were labeled with radioiodine for characterization. The immunoreactivity of the conjugates, determined in a direct binding assay on CEA coupled to sepharose, was not modified by the coupled AlPcS4A1 molecules. In vivo, these conjugates were evaluated in nude mice bearing human colon carcinoma xenografts (T380). 35A7 MAb-(AlPcS4A1)5, 35A7 MAb-(AlPcS4A1)12 and 35A7 MAb-(AlPcS4A1)16 conjugates displayed a tumor uptake of 35 +/- 5.0%, 40 +/- 5.7% and 32 +/- 3.3% of the injected dose per gram of tumor tissue, respectively, corresponding to an uptake of 97%, 104% and 91% as compared to that of the unconjugated 35A7 MAb. In each experimental group, the tumor-to-normal tissue ratios obtained with the conjugates were almost identical to those obtained with unconjugated 35A7 MAb. Average values of 1.8, 7 and about 30 were obtained for blood, liver and muscle, respectively. Phototoxic efficacy of the 35A7 MAb-(AlPcS4A1)12 conjugate was demonstrated in vitro on the LoVo cell line giving a 91% growth inhibition for a 2.50 micrograms/mL AlPcS4A1 concentration. We conclude that these conjugates demonstrate clear in vivo tumor-seeking capacity and in vitro photocytotoxic properties. Such conjugates could thus be promising candidate drugs for clinical photodynamic therapy of cancers expressing CEA.

Topics: Animals; Antibodies, Monoclonal; Carcinoembryonic Antigen; Colonic Neoplasms; Fluorescent Dyes; Humans; Immunotoxins; Indoles; Mice; Mice, Nude; Neoplasm Transplantation; Organometallic Compounds; Radiation-Sensitizing Agents; Tissue Distribution; Transplantation, Heterologous; Tumor Cells, Cultured

Topics: Animals; Brain Neoplasms; Colonic Neoplasms; Cricetinae; Female; Indoles; Male; Mesocricetus; Mice; Organometallic Compounds; Pancreatic Neoplasms; Photochemotherapy; Rats; Rats, Inbred Strains