INTRACELLULAR UPTAKE, ABSORPTION-SPECTRUM AND STABILITY OF THE BACTERIOCHLORIN PHOTOSENSITIZER 5,10,15,20-TETRAKIS(M-HYDROXYPHENYL) BACTERIOCHLORIN (MTHPBC) - COMPARISON WITH 5,10,15,20-TETRAKIS(M-HYDROXYPHENYL) CHLORIN (MTHPC)

The bacteriochlorin photosensitizer 5,10,15,20-tetrakis (m-hydroxyphen yl) bacteriochlorin (mTHPBC) is a member of a series of related compou nds which includes the well-known compound 5,10,15,20-tetrakis(m-hydro xyphenyl)chlorin(mTHPC) (temoporfin). Although this bacteriochlorin ha s near-ideal spectral characteristics in pure solvents, little is know n of its stability or other characteristics within tumour cells. This study compares mTHPBC with mTHPC in both solvents in vitro and monolay ers of the mouse colon tumour cell line Colo26. In aqueous protein-con taining solvents, mTHPBC shows signs of aggregation and is oxidized to mTHPC at a rate of 2% h(-1). Both drugs are taken up by the cells at similar rates and to the same extent, with plateau levels being reache d between 9 and 30 h of incubation. Between 25% and 33% of the bacteri ochlorin within the cells is oxidized to chlorin in 24 h, after which no further net oxidation is observed. The intracellular absorption spe ctra suggest that mTHPBC exists in more than one form within the cells . Measurements of photodynamic therapy (PDT) activity confirm that mTH PBC is active within these cells, but with between 0.6 and 0.7 of the potency of mTHPC. Although aggregation and oxidation of the bacterioch lorin will reduce its overall effectiveness, this must be balanced aga inst the potential effect of the greater red light penetration in vivo and the presence of a green light peak which may be employed to treat thin lesions where there is a risk of perforation of a hollow organ. (C) 1997 Elsevier Science S.A.