Photodynamic therapy effect of m-THPC (Foscan) in vivo: correlation with pharmacokinetics.
m-Tetra(hydroxyphenyl)chlorin (m-THPC, Foscan, Temoporfin) has an unusually high photodynamic efficacy which cannot be explained by its photochemical properties alone. In vivo interactions are therefore of critical importance in determining this high potency. The pharmacokinetics of m-THPC in a rat tumour model was determined using (14)C m-THPC in an LSBD(1) fibrosarcoma implanted into BDIX rats. The photodynamic therapy (PDT) efficacy was determined at different drug administrations to light intervals and correlated with the tumour and plasma pharmacokinetic data. The plasma pharmacokinetics of m-THPC can be interpreted by compartmental analysis as having three half-lives of 0.46, 6.91 and 82.5 h, with a small initial volume of distribution, suggesting retention in the vascular compartment. Tissues of the reticuloendothelial system showed high accumulation of m-THPC, particularly the liver. PDT efficacy of m-THPC over the same time course seemed to exhibit two peaks of activity (2 and 24 h), in terms of tumour growth delay with the peak at 24 h postinjection correlating to the maximum tumour concentration. Investigation on tumour cells isolated from m-THPC-treated tumours suggested that the peak PDT activity at 2 h represents an effect on the vasculature while the peak at 24 h shows a more direct response. These results indicate that the in vivo PDT effect of m-THPC occurs via several mechanisms.
Jones
H J
HJ
DI Vernon School of Biochemistry and Molecular Biology, Centre for Photobiology and Photodynamic Therapy, University of Leeds, Leeds LS2 9JT, UK. d.i.vernon@leeds.ac.uk
Vernon
D I
DI
Brown
S B
SB
D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005354:Fibrosarcoma / Q000188:drug therapy; D006207:Half-Life; D007700:Kinetics; D008297:Male; D008652:Mesoporphyrins / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009374:Neoplasms, Experimental; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin