This paper describes the photodynamic characteristics of the new near-infrared
photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (
mTHPBC or
SQN400) in normal rat and mouse tissues. A rat liver model of photodynamic tissue
necrosis was used to determine the in vivo action spectrum and the dose-response relationships of tissue destruction with
drug and light doses. The effect of varying the light irradiance and the time interval between
drug administration and light irradiation on the
biological response was also measured in the rat liver model. Photobleaching of
mTHPBC was measured and compared with that of its
chlorine analog (
mTHPC) in normal mouse skin and an implanted mouse
colorectal tumor. The optimum wavelength for
biological activation of
mTHPBC in rat liver was 739 nm.
mTHPBC was found to have a marked
drug-dose threshold of around 0.6 mg kg-1 when liver tissue was irradiated 48 h after
drug administration. Below this administered
drug dose, irradiation, even at very high light doses, did not cause liver
necrosis. At administered doses above the photodynamic threshold the effect of
mTHPBC-
PDT was directly proportional to the product of the
drug and light doses. No difference in the extent of liver
necrosis produced by
mTHPBC was found on varying the light irradiance from 10 to 100 mW cm-2. The extent of liver
necrosis was greatest when tissue was irradiated shortly after
mTHPBC administration and
necrosis was absent when irradiation was performed 72 h or later after
drug administration, suggesting that the
drug was rapidly cleared from the liver. In vivo photobleaching experiments in mice showed that the rate of bleaching of
mTHPBC was approximately 20 times greater than that of
mTHPC. It is argued that this greater rate of bleaching accounts for the higher photodynamic threshold and this could be exploited to enhance selective destruction of tissues which accumulate the
photosensitizer.