Evaluation of porfimer sodium in dogs and cats with spontaneous tumors.

The effect of photodynamic therapy is a function of several variables, including selective retention of the drug in tumor tissue with reduced drug concentration in surrounding normal tissue. A study was designed to determine the pharmacokinetic profile and variability of porfimer sodium in dogs and cats with spontaneous tumors and to thereby determine the optimal timing of its photoactivation in these species. The results of this study indicate that there is marked variability among species in the distribution of porfimer sodium between highly proliferating tissues, which requires careful attention in the design of human and veterinary application of photodynamic therapy with porfimer sodium, as determined in rodent models.

Biodistribution of three photosensitizers in dogs with spontaneous tumors.

Photodynamic therapy (PDT) has been considered a potential method for tumor eradication. The present study was designed to assess the efficacy of PDT as an alternative treatment approach. Photosensitizers, such as porfimer sodium, tin ethyl etiopurpurin, and aluminum chlorophthalocyanine, were administered i.v. to dogs, and tissue samples were harvested 24 to 300 hours later. The uptake of the photosensitizers in tumor (fibrosarcoma) and adjacent normal tissue biopsies was quantified by tissue solubilization technique and fluorimetry. In addition, the pharmacokinetics and selectivity of the photosensitizers were addressed by two-phase exponential function and specific uptake ratio, respectively. Porfimer sodium exhibited a longer elimination half-life (175.3 hr), slower clearance (0.0028 L/kg/hr), and a larger area under the curve (1075 microg/g/hr) in tumors than did tin ethyl etiopurpurin or aluminum chlorophthalocyanine. As a result, porfimer sodium showed a good selectivity in tumors located in muscle and skin. The study provided clinical information for determination of the efficacy of different PDT alternatives.

Threshold dose of three photosensitizers in dogs with spontaneous tumors.

Photodynamic threshold doses in dogs with spontaneous tumors can be achieved through a mathematical model. For this to be clinically relevant, it is important to know the treatment parameters for tissue necrosis. The threshold dose for three photosensitizers (porfimer sodium, aluminum cholorophthalocyanine [AlClPc], and tin ethyl etiopurpurin [SnET2]) commonly used in veterinary chemotherapy protocols was evaluated in 12 dogs with spontaneous tumors. To derive the photodynamic threshold dose, the tissue optical properties of each compound were determined by diffuse reflectance and thus the light fluence rate. Uptake was measured by fluorimetry using tissue solubilization techniques. The threshold values calculated were highest for AlClPc (irradiated 48 hours after administration). The radius of necrosis (4.00 to 5.48 mm) and photosensitizer uptake (3.4 to 6.91 microg/g) were elevated after injection of porfimer sodium. The threshold dose model described here is photosensitizer dependent but independent of photosensitizer uptake and light dose. This study indicates that more photon absorption is needed for tumor necrosis with AlClPc than for either SnET2 or porfimer sodium.