Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currentl y under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assesse d damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rat s with chondrosarcoma were given 2 mg kg(-1) of BPD intravenously 5 min to 180 min before light treatment of 150 J cm(-2) 690 nm. Vascular response wa s monitored using intravital microscopy and tumour cure was monitored by fo llowing regrowth over 42 days. For treatment at 5 or 30 min after BPD injec tion, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective t argeting for damage. No acute changes were observed in vessels when light w as given 180 min after BPD injection. Tumour regression after light treatme nt occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in anima ls given treatment 180 min after drug injection. The correlation between th e timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction.