A new drug-screening procedure for photosensitizing agents used in photodynamic therapy for CNV.
OBJECTIVE
Because vascular occlusion has been observed as a consequence of photodynamic therapy (PDT), this method has been successfully used for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). However, most conventional photosensitizers, primarily developed for tumor PDT, lack selectivity for the targeting of neovascularization. An experimental model has been developed for drug screening of new photosensitizers for the treatment of CNV associated with AMD. It consists of intravenous (IV) injection of photosensitizers and fluorescent dyes into the chick's chorioallantoic membrane (CAM), followed by measurement of fluorescence pharmacokinetics, leakage from the vascular system, and photothrombic efficacy.


METHODS
Fertilized chicken eggs were placed under a fluorescence microscope. After intravenous injection of different dyes, time-dependent fluorescence angiography was performed. The effect of PDT parameters was assessed by fluorescence angiography 24 hours after PDT.


RESULTS
Although fluorescence of lipophilic benzoporphyrin derivative monoacid ring A (BPD-MA) remained intravascular during 2 hours, hydrophilic dyes tended to leak through the fenestrated neovascularization. By variation of PDT parameters, vascular damage could be directed toward closure of vessels with a diameter smaller than 10 microm, as measured 24 hours after PDT. High photosensitizer concentrations and high light doses resulted in blood flow stasis within 60 minutes, confirmed by fluorescence angiography.


CONCLUSIONS
Fluorescence angiography and PDT after IV injection into the CAM showed strong similarities to results obtained in clinical tests of PDT in CNV associated with AMD. Thus, this model can provide valuable information about PDT mechanisms and can be used for drug-screening purposes in development of improved sensitizers for the PDT of CNV.
Lange
N
N
Institute of Environmental Engineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland. norbert.lange@epfl.ch
Ballini
J P
JP
Wagnieres
G
G
van den Bergh
H
H
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D000818:Animals; D002199:Capillary Permeability; D002642:Chick Embryo / Q000098:blood supply*; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005451:Fluorescein Angiography; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D012235:Rhodamines / Q000008:administration & dosage / Q000493:pharmacokinetics
D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011166:Porphyrins; D012235:Rhodamines; C504224:benzoporphyrin D; C050829:sulforhodamine 101