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- Author or Editor: Margaret A. Miller x
- Oncology x
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Abstract
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.
Abstract
Objective—To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs.
Sample—10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma.
Procedures—Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis.
Results—FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild.
Conclusions and Clinical Relevance—This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.
