Preclinical evaluation of zinc phthalocyanine tetrasulfonate-based PDT

摘要

Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS_4) is a promising second-generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available. ZnPcS_4 was given to Swiss Webster mice to assess acute toxicity. Doses > 100 mg/kg were associated with acute toxicity and mortality, and doses > 100 mg/kg resulted in renal tubular nephrosis, suggesting that the minimum toxic dose is approximately 100 mg/kg. Based on these data, a Phase I clinical trial of ZnPcS_4-based PDT in tumor-bearing dogs is underway, with ZnPcS_4 doses up to 2 mg/kg producing no apparent toxicity. Tumor response has been observed after ZnPcS_4-based PDT using doses as low as 0.25 mg/kg, suggesting that conventional phase Ⅰ clinical trials may not be appropriate for PDT protocols.