Trong nghiên cứu in vitro bằng cách sử dụng các dòng tế bào khối u khác nhau đã chỉ ra rằng nhạy liên hợp với các kháng thể đơn dòng có thể đạt được một hiệu quả cao phototoxic ở liều thấp hơn so với thuốc hoặc kháng thể một mình (44,45). Trong công việc cơ thể sống trong một mô hình rhabomyosarcoma chuột mang lại kết quả tương tự | 138 Kim and Miller PDT as a therapeutic modality. Antibody-based targeting is one method currently under investigation. In vitro studies using various tumor cell lines have shown that photosensitizers conjugated to monoclonal antibodies can achieve a higher phototoxic effect at lower doses than with drug or antibody alone 44 45 . In vivo work in a mouse rhabomyosarcoma model yielded similar results 46 . While direct attachment of photosensitizing drugs to monoclonal antibodies is possible the number of molecules that can be bound to one antibody is limited due to loss of or alterations in antigenic specificity. The use of spacers such as dextran polyglutamic acid or polyvinyl alcohol PVA has been proposed to address these issues 47 . This method of conjugation allows high molar ratios of drug to antibody while conferring water-solubility to the final compound. Jiang et al. 44 linked BPD to 5E8 a monoclonal antibody against a cell-surface glycoprotein using PVA and demonstrated 15-fold higher phototoxicity with the conjugate than with BPD alone. For current ocular applications the intended target for photosensitizer delivery is the neovascular endothelium. One strategy is to bind the photosensitizer to a molecule directed at binding sites on the CNV endothelium such as VEGF receptors or integrins. Work in our laboratory focused on a peptide ATWLPPR which has been shown to bind specifically to the VEGFR2 receptor also known as KDR or FLK-1. This peptide completely inhibits VEGF binding to VEGFR2 48 . We produced a targeted photosensitizer by binding verteporfin to a PVA linker and then to the homing peptide ATWLPPR 49 . For controls we used verteporfin-PVA which is a large but untargeted molecule and also commercially available verteporfin. In vivo experiments were carried out in the laser-injury model of CNV in the rat for which dosimetry for verteporfin PDT has been optimized 50 . We found that PDT using both targeted verteporfin and verteporfin-PVA were effective
