Safety of zinc phthalocyanine photodynamic therapy for tumors in dogs

Abstract

OBJECTIVE: To determine the threshold for acute toxicosis of parenterally administered zinc phthalocyanine tetrasulfonate (ZnPcS(4)), a candidate second-generation photosensitizer, in mice and evaluate the compound's safety in a phase I clinical trial of ZnPcS(4)-based photodynamic therapy (PDT) in pet dogs with naturally occurring tumors. ANIMALS: Male Swiss-Webster mice and client-owned dogs with naturally occurring neoplasms. PROCEDURES: For the study of acute toxicosis, mice were given graded doses of ZnPcS(4). To determine safety, a rapid-titration phase I clinical trial of ZnPcS(4)-based PDT in tumor-bearing dogs was conducted. RESULTS: In mice, administration of >or= 100 mg of ZnPcS(4)/kg resulted in renal tubular necrosis 24 hours after IP injection. In tumor-bearing dogs, ZnPcS(4) doses <or= 4 mg/kg induced no signs of toxicosis and resulted in partial to complete tumor responses in 10 of 12 dogs 4 weeks after PDT. Tumor remission was observed with ZnPcS(4) doses as low as 0.25 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: A conservative starting dose of ZnPcS(4) was arrived at on the basis of mouse toxicosis findings. Zinc phthalocyanine tetrasulfonate-based PDT was tolerated well by all dogs and warrants further study. The identification of the maximum tolerated dose through traditional phase I clinical trials may be unnecessary for evaluating novel PDT protocols.