Optimizing photodynamic therapy: in vivo pharmacokinetics of liposomal meta-(tetrahydroxyphenyl)chlorin in feline squamous cell carcinoma.
OBJECTIVE
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.


METHODS
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 approximately 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.
Buchholz
Julia
J
Section of Diagnostic Imaging and Radiation Oncology, Vetsuisse Faculty, and Biostatistics, Institut für Sozial- und Präventivmedizin, University of Zurich, Switzerland. jbuchholz@vetclinics.unizh.ch
Kaser-Hotz
Barbara
B
Khan
Tania
T
Rohrer Bley
Carla
C
Melzer
Katja
K
Schwendener
Reto A
RA
Roos
Malgorzata
M
Walt
Heinrich
H
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002415:Cats; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry; D008652:Mesoporphyrins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008657:Metabolic Clearance Rate; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin