ASSESSMENT OF THE CYTOTOXICITY OF THE PHOTOSENSITIZING DRUG BPD VERTEPORFIN USING HUMAN VASCULAR SMOOTH-MUSCLE CELLS IN CULTURE

Photosensitizing drugs are selectively taken up by lipid-rich lesions such as atheromatous plaque which when exposed to light render the dru gs cytotoxic. However, skin photosensitivity which persists for many w eeks is a significant side effect, We investigated the cytotoxicity of a new photosensitizing drug, the benzoporphyrin derivative BPD vertep orfin (Quadra Logic Technologies), which does not have this deleteriou s side effect, Vascular smooth muscle cells (VSMC) from normal human m ammary and diseased human coronary arteries were grown in culture from explants and characterized with respect to their growth rates. The se nsitivity to BPD with and without light was assessed by measuring viab ility after treatment. The lethal dose of drug for 50% viability loss (LD(50)) for BPD with light was similar to 12.5 ng/ml for mammary arte ry, with 52 +/- 8% cell survival (n = 6). The coronary artery VSMC fro m all patient sources, although differing significantly in growth rate , had a survival of 44 +/- 6% (n = 12) at the same concentration of BP D used for the mammary artery SMC (p = NS). Our results established th e LD(50) for BPD using human arterial sources of SMC and showed that t he growth rates of the cells did not affect the cytotoxicity of the dr ug.