FOSCAN-MEDIATED PHOTODYNAMIC THERAPY FOR A PERITONEAL-CANCER MODEL - DRUG DISTRIBUTION AND EFFICACY STUDIES

Distribution of the photosensitizer Foscan(R) (meta-tetrahydroxyphenyl chlorin, mTHFC), after i.v. or i.p. injection, was investigated in Wag /Rij rats bearing i.p. tumours. These results were com pared with the efficacy of mTHPC-mediated photodynamic therapy for illumination inter vals of 4 hr to 3 days, For the distribution experiments a single tumo ur (CC531 colon carcinoma) was implanted intra-abdominally in a fat pa d, or a cell suspension (1 x 10(6) CC531 cells) was injected into the peritoneal cavity, which results in a dissemination of tumour nodules on the peritoneum. C-14-mTHPC was not selectively taken up in the sing le-tumour model after i.v. or i.p. injection, but higher concentration s were achieved for i.p. administration, For this tumour model the con centration ratios between tumour and normal tissue never exceeded a va lue of 3, In the disseminated-tumour model, an uptake of up to 40% of the injected dose was found per gram tumour at 4 hr after an i.p. inje ction and this resulted in very high (> 14) concentration ratios of tu mour to normal tissues. Low uptake was found after the i.v. injection route (1% of the injected dose per gram tumour) with lower tumour/norm al tissue ratios (< 8). The efficacy of i.p. photodynamic therapy (IP- PDT) was evaluated using the single-tumour model only. The lower abdom en was illuminated at 4 hr to 3 days after mTHPC, and tumour size was repeatedly measured via a small laparoscopy, Significant delay in tumo ur regrowth was achieved for 6 J.cm(-2) at 1 day after i.v., or at 4 h r after i.p. mTHPC (p values 0.019 and 0.045 respectively), Response t o PDT, of tumours implanted in the fat pad, was not greater for i.p. a dministration of the photosensitizer and there was a poor correlation between times of maximum drug uptake in tumours and optimal illuminati on times for PDT efficacy. (C) 1997 Wiley-Liss, Inc.