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Optimizing Photodynamic Therapy: In vivo Pharmacokinetics of Liposomal meta-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma

Authors' Affiliations: ¹ Section of Diagnostic Imaging and Radiation Oncology, Vetsuisse Faculty, and ² Biostatistics, Institut für Sozial- und Präventivmedizin, University of Zurich; ³ Research Division of Gynecology, Department of Gynecology, University Hospital Zurich, Zurich, Switzerland and ⁴ Molecular Cell Biology, Paul Scherrer Institute, Villigen, Switzerland

Requests for reprints: Julia Buchholz, Section of Diagnostic Imaging and Radiation Oncology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland. Phone: 41-1-635-8744; Fax: 41-1-635-8940; E-mail: jbuchholz{at}vetclinics.unizh.ch.

Purpose: The aim of the present study was to optimize and simplify photodynamic therapy using a new liposomal formulation of the photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan); liposomal m-THPC (Fospeg)] and to reduce systemic reactions to the photosensitizer.

Experimental Design: To examine the pharmacokinetics of liposomal m-THPC, we determined tissue and plasma variables in feline patients with spontaneous squamous cell carcinoma. In vivo fluorescence intensity measurements of tumor and skin were done with a fiber spectrophotometer after i.v. injection of m-THPC or liposomal m-THPC in 10 cats. Blood samples, drawn at several time points after photosensitizer administration, were analyzed by high-performance liquid chromatography.

Results: None of the liposomal m-THPC–treated cats showed side effects during or after drug injection. Fluorescence intensities, fluorescence ratios (tumor fluorescence divided by skin fluorescence), and bioavailability in the tumor were 2 to 4 times higher with liposomal m-THPC compared with m-THPC. Liposomal m-THPC concentration in the tumor increased constantly to reach a maximum at 4 hours after injection. Plasma concentration and bioavailability were 3 times higher with liposomal m-THPC compared with m-THPC measured at the time points of highest plasma concentration. The distribution half-life was shorter with liposomal m-THPC, resulting in maximal tumor accumulation up to 5.5 times earlier. Maximal tumor accumulation and maximal fluorescence ratio with liposomal m-THPC occurred at the same time point, indicating maximal selectivity. In both groups, all cats responded to therapy.

Conclusions: Liposomal m-THPC was well tolerated by all cats and seems to have superior pharmacokinetic properties compared with m-THPC. The efficacy of the drug warrants further study.