Objective—To determine whether transitional cell
carcinoma (TCC) cells incubated in media containing
5-aminolevulinic acid (ALA) would produce sufficient
protoporphyrin IX (PpIX) to cause lethal phototoxic
effects when exposed to 635-nm light.
Sample Population—Canine TCC cells (K9TCC).
Procedure—Cultured K9TCC cells were exposed to
graded doses of ALA, and PpIX concentrations were
determined. Cells then were exposed to various
doses of 635-nm light from a diode laser, and cell viability
Results—Production of PpIX was dependent on time
and dose of ALA. The K9TCC cells incubated with ALA
produced sufficient PpIX to cause lethal phototoxic
effects when exposed to 635-nm light. Phototoxic
effects were dependent on time and dose of ALA.
Increasing laser power density and energy density
decreased cell survival.
Conclusions and Clinical Relevance—ALA is an
effective photosensitizer for in vitro photodynamic
treatment of K9TCC cells. Further studies are warranted
to assess the safety and efficacy of ALA as a
photosensitizer for use in treating dogs with TCC.
Impact for Human Medicine—On the basis of this
study, dogs with TCC may be useful in the development
of protocols for ALA-based photodynamic therapy
of humans affected with muscle-invasive bladder
cancer. (Am J Vet Res 2003;64:131–136)
Objective—To determine the threshold for acute toxicosis of parenterally administered zinc phthalocyanine tetrasulfonate (ZnPcS4), a candidate second-generation photosensitizer, in mice and evaluate the compound's safety in a phase I clinical trial of ZnPcS4-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 ZnPcS4. To determine safety, a rapid-titration phase I clinical trial of ZnPcS4-based PDT in tumor-bearing dogs was conducted.
Results—In mice, administration of ≥ 100 mg of ZnPcS4/kg resulted in renal tubular necrosis 24 hours after IP injection. In tumor-bearing dogs, ZnPcS4 doses ≤ 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 ZnPcS4 doses as low as 0.25 mg/kg.
Conclusions and Clinical Relevance—A conservative starting dose of ZnPcS4 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.