Time-dependent photodynamic damage to blood vessels: correlation with serum photosensitizer levels

We have used the technique of dynamic capillaroscopy to study the time-course of photodynamic vascular occlusion in mice injected intraperitoneally with either of two photosensitizers; hematoporphyrin esters (HPE) or meso-tetrahydroxyphenyl chlorin (mTHPC). The peak of vascular occlusion induced by HPE coincided in time with peak serum levels of this photosensitizer (about 3 h after injection). However, there was also a second peak of occlusive activity at about 12 h after injection, at which time serum HPE was falling monotonically. In the case of mTHPC, no peak of occlusive activity was seen at 3 h after injection, even though the serum levels of this photosensitizer, like those of HPE, were highest around this time. Instead, a steady rise in photosensitizing activity was observed, peaking at 11 h. This decoupling between serum drug levels and vascular photosensitization--partial for HPE and complete for mTHPC-suggests that direct photosensitization of endothelial cells is unlikely wholly to explain the vascular collapse. Instead, there must be either another compartment that accumulates photosensitizer more slowly and in which photodynamic activity has an indirect effect on the blood capillaries or a slow metabolic transformation of mTHPC into a more active sensitizer.