Targeted PDT more effective in stopping leakage at fraction of dose of standard PDT in rat model

May 6, 2009

Factor VII (fVII)-verteporfin (Visudyne, Novartis) for targeted photodynamic therapy (PDT) significantly reduced leakage compared with non-targeted PDT in a rat model of choroidal neovascularization. The dose that was efficacious was about 1/10 that of the standard dose of PDT, said Ron Adelman, MD, MPH, Department of Ophthalmology, Yale University Eye Center, New Haven, CT.

Fort Lauderdale, FL-Factor VII (fVII)-verteporfin (Visudyne, Novartis) for targeted photodynamic therapy (PDT) significantly reduced leakage compared with non-targeted PDT in a rat model of choroidal neovascularization. The dose that was efficacious was about 1/10 that of the standard dose of PDT, said Ron Adelman, MD, MPH, Department of Ophthalmology, Yale University Eye Center, New Haven, CT.

“Standard PDT is not selective against abnormal blood vessels,” he said. “Standard PDT affects normal and abnormal vessels.”

However, fVII-verteporfin binds tightly and specifically to tissue factor, which is expressed on endothelial cells of CNV but not normal vasculature.

Dr. Adelman and associates conducted an experimental rat model of laser-induced CNV. Three weeks after the laser treatment, the rats were injected with either fVII-verteporfin in one of two doses (0.5 mg/m² or 1 mg/m²) or with standard verteporfin (6 mg/m²).

Targeted PDT showed higher efficacy in stopping leakage in this rat model of CNV using 1/10 of the dose compared with standard PDT, Dr. Adelman said. In the rats with standard PDT injected, leakage was observed in 75% and 100% of lesions on days 7 and 14, respectively. In contrast, in the rats with the lower dose of targeted PDT injected, the respective rates of leakage were 33% and 36%. In the rats that received the higher dose of targeted PDT, the respective rates of leakage were 25% and 23%.

“This indicated that the efficacy with targeted PDT at 1/10 the standard dose was three times greater compared with standard PDT,” Dr. Adelman said.

He also reported that there was a significant decrease in ischemia associated with targeted PDT.

“Targeted PDT seems to be a promising treatment for neovascular disorders of the choroid and retina,” he concluded. “This technology has the potential to enhance other antiangiogenic treatments such as for abnormal blood vessels. Application to the treatment of skin cancer is under investigation.”