Does tumour uptake of Foscan determine PDT efficacy?
Preferential retention of photosensitizers in tumours has always been one of the major goals in the search for new photosensitizers and has determined the design of clinical trials with respect to the interval between drug administration and illumination. The purpose of this study was to investigate the importance of tumour and plasma concentrations of Foscan (mTHPC, meta-tetrahydroxyphenylchlorin) in relation to PDT effect. Both pharmacokinetic and tumour response studies were carried out in mice bearing s.c. RIF1 tumours. mTHPC was injected in 1 or 2 doses of 0.3 mg x kg-1. For distribution studies, 14C-labelled mTHPC was given 5 min to 48 hr before determination of plasma and tumour drug levels. Non-labelled sensitizer was used to determine the PDT efficacy for illumination at 5 min to 48 hr after drug administration. PDT efficacy was greatest for illumination at 1 to 3 hr, and for an interval of 48 hr there was no significant tumour-growth delay. In contrast, mTHPC tumour drug levels reached a maximum 6 hr after injection and remained high for 48 hr. A comparison of pharmacokinetics and response studies revealed no significant correlation between tumour mTHPC levels and tumour response. There was, however, a significant correlation between plasma drug levels and tumour response for time intervals of 1 to 48 hr. This association may imply that PDT protocols should use shorter drug-light intervals in combination with lower drug doses. This would increase safety and decrease the extent and duration of normal tissue photosensitization.
Veenhuizen
R
R
Experimental Therapy Division, Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam, The Netherlands.
Oppelaar
H
H
Ruevekamp
M
M
Schellens
J
J
Dalesio
O
O
Stewart
F
F
D000818:Animals; D002250:Carbon Radioisotopes / Q000627:therapeutic use; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007275:Injections, Intravenous; D008652:Mesoporphyrins / Q000493:pharmacokinetics*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured
D002250:Carbon Radioisotopes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin