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)

Abstract

The bacteriochlorin photosensitizer 5,10,15,20-tetrakis ( m-hydroxyphenyl) bacteriochlorin (mTHPBC) is a member of a series of related compounds which includes the well-known compound 5,10,15,20-tetrakis ( m-hydroxyphenyl) chlorin (mTHPC) (temoporfin). Although this bacteriochlorin has near-ideal spectral characteristics in pure solvents, little is known of its stability or other characteristics within tumour cells. This study compares mTHPBC with mTHPC in both solvents in vitro and monolayers of the mouse colon tumour cell line Colo26. In aqueous protein-containing 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 reached between 9 and 30 h of incubation. Between 25% and 33% of the bacteriochlorin within the cells is oxidized to chlorin in 24 h, after which no further net oxidation is observed. The intracellular absorption spectra suggest that mTHPBC exists in more than one form within the cells. Measurements of photodynamic therapy (PDT) activity confirm that mTHPBC is active within these cells, but with between 0.6 and 0.7 of the potency of mTHPC. Although aggregation and oxidation of the bacteriochlorin will reduce its overall effectiveness, this must be balanced against 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.