A new drug-screening procedure for photosensitizing agents used in photodynamic therapy for CNV

PURPOSE, Because vascular occlusion has been observed as a consequence of p hotodynamic therapy (PDT), this method has been successfully used for the t reatment of choroidal neovascularization (CNV) in age-related macular degen eration (AMD). However, most conventional photosensitizers, primarily devel oped for tumor PDT, lack selectivity for the targeting of neovascularizatio n. an experimental model has been developed for drug screening of new photo sensitizers for the treatment of CNV associated with AMD. It consists of in travenous (IV) injection of photosensitizers and fluorescent dyes into the chick's chorioallantoic membrane (CMI), followed by measurement of fluoresc ence pharmacokinetics, leakage from the vascular system, and photothrombic efficacy. METHODS. Fertilized chicken eggs were placed under a fluorescence microscop e. after intravenous injection of different dyes, time-dependent fluorescen ce angiography was performed. The effect of PDT parameters was assessed by fluorescence angiography 24 hours after PDT. RESULTS. Although fluorescence of lipophilic benzoporphyrin derivative mono acid ring A (BPD-MA) remained intravascular during 2 hours, hydrophilic dye s tended to leak through the fenestrated neovascularization. By variation o f PDT parameters, vascular damage could be directed toward closure of vesse ls with a diameter smaller than 10 mum, as measured 24 hours after PDT. Hig h photosensitizer concentrations and high light doses resulted in blood flo w stasis within 60 minutes, confirmed by fluorescence angiography. CONCLUSIONS. Fluorescence angiography and PDT after TV injection into the C AM showed strong similarities to results obtained in clinical tests of PDT in CNV associated with AMD. Thus, this model can provide valuable informati on about PDT mechanisms and can be used for drug-screening purposes in deve lopment of improved sensitizers for the PDT of CNV.