Significance of dosimetry in photodynamic therapy of injured arteries: Classification of biological responses

With conflicting results in the literature on the ability of photodynamic t herapy (PDT) to inhibit intimal hyperplasia (IH), the present study systema tically investigated the effects of drug and light dosimetry on the biologi c responses in the artery wall. The rat common carotid artery was balloon-i njured and pressurized with benzoporphyrin-derivative monoacid ring (BPD), Then, PDT was performed with an external laser at different fluences and th e biologic responses of the artery wall were histologically examined at 24 h and at 2 weeks, Photodynamic therapy effects on injured arteries can be c lassified into four stages: low-dose PDT using 0.5 mu g/mL BPD at 50 J/cm(2 ) (stage I) resulted in incomplete cell eradication and significant LH at 2 weeks. Irradiation with 100 J/cm(2) at the same BPD concentration (stage I I) completely eradicated the cells in the artery wall at 24 h but still led to IH at 2 weeks, However, 25 mu g/mL BPD at 100 J/cm(2) (stage IH) result ed in total cell eradication at 24 h and inhibition of IH at 2 weeks, In co ntrast, high-dose PDT with 25 mu g/mL BPD and 200 J/cm(2) (stage IV) led to thrombus development and vascular occlusion at 24 h, These data, demonstra ting the different stages of PDT effects on injured arteries, emphasize the critical importance of appropriate PDT dosimetry for the effective inhibit ion of IH.