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Foscan‐mediated photodynamic therapy for a peritoneal‐cancer model: Drug distribution and efficacy studies
Author(s) -
Veenhuizen Ruth B.,
Ruevekamp Marjan C.,
Oppelaar Hugo,
Helmerhorst Theo J.M.,
Kenemans Peter,
Stewart Fiona A.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971009)73:2<230::aid-ijc12>3.0.co;2-j
Subject(s) - photodynamic therapy , photosensitizer , medicine , distribution (mathematics) , peritoneal cavity , peritoneum , chemotherapy , chlorin , pathology , urology , nuclear medicine , surgery , chemistry , mathematical analysis , mathematics , organic chemistry
Distribution of the photosensitizer Foscan® (meta‐tetrahydroxyphenylchlorin, mTHPC), after i.v. or i.p. injection, was investigated in Wag/Rij rats bearing i.p. tumours. These results were compared with the efficacy of mTHPC‐mediated photodynamic therapy for illumination intervals of 4 hr to 3 days. For the distribution experiments a single tumour (CC531 colon carcinoma) was implanted intra‐abdominally in a fat pad, or a cell suspension (1 × 10 6 CC531 cells) was injected into the peritoneal cavity, which results in a dissemination of tumour nodules on the peritoneum. 14 C‐mTHPC was not selectively taken up in the single‐tumour model after i.v. or i.p. injection, but higher concentrations were achieved for i.p. administration. For this tumour model the concentration ratios between tumour and normal tissue never exceeded a value 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. injection and this resulted in very high (>14) concentration ratios of tumour to normal tissues. Low uptake was found after the i.v. injection route (1% of the injected dose per gram tumour) with lower tumour/normal tissue ratios (<8). The efficacy of i.p. photodynamic therapy (IPPDT) was evaluated using the single‐tumour model only. The lower abdomen was illuminated at 4 hr to 3 days after mTHPC, and tumour size was repeatedly measured via a small laparoscopy. Significant delay in tumour regrowth was achieved for 6 J · cm −2 at 1 day after i.v., or at 4 hr after i.p. mTHPC ( p values 0.019 and 0.045 respectively). Response to PDT, of tumours implanted in the fat pad, was not greater for i.p. administration of the photosensitizer and there was a poor correlation between times of maximum drug uptake in tumours and optimal illumination times for PDT efficacy. Int. J. Cancer 73:230–235, 1997. © 1997 Wiley‐Liss, Inc.