In vitro and in vivo photodynamic effects of a new photosensitizer: Tetra(m-hydroxyphenyl)chlorin

The photodynamic effects of a new photosensitizer, meso-tetra(hydroxyphenyl) chlorin (m-THPC), and Photofrin were evaluated and compared in in vitro and in vivo experiments. For in vitro assays, the influence of sensitizer doses and incubation time on the toxicity and phototoxicity of murine leukaemic cells (L1210) were studied. For in vivo assays, the influence of sensitizer and laser doses on the growth of a human tumour (HT29) originated from a human colorectal adenocarcinoma (grafted subcutaneously in mice) were studied. For in vitro assays, LD50 was reached at 1 μg ml−1 for Photofrin and 0.88 μg ml−1 for m-THPC after 2-h incubation on leukaemic cells irradiated at 514 nm with an energy density of 25 J cm−2. When incubation time was increased, m-THPC-induced photoxicity increased more than Photofrin photoxicity. In vivo, at an energy density of 40 J cm−2, m-THPC (0.25, 0.5 mg kg−1) irradiated at 650 nm was more potent than Photofrin (5 mg kg−1) irradiated at 632 nm but was also more phototoxic to mice. Laser doses seemed to have less influence than m-THPC doses on tumour growth as the tumour growth index was 12 mm at a laser dose of 10 J cm−2 and 13 mm at 40 J cm−2 (21.4 mm for control,p<0.01). It is likely that the greater efficiency of m-THPC was due in part to a higher quantum yield of1O2 for m-THPC than for Photofrin and to better light transmission at 650 nm in living tissues than at 630 nm. However, microscopic m-THPC distribution throughout tumour sites has to be precise.