Systemic application of photosensitizers in the chick chorioallantoic membrane (CAM) model: photodynamic response of CAM vessels and 5-aminolevulinicacid uptake kinetics by transplantable tumors

The aim of this study is to modify the chick chorioallantoic membrane (CAM) model into a whole-animal tumor model for photodynamic therapy (PDT). By u sing intraperitoneal (IP) photosensitizer injection of the chick embryo, us e of the CAM for PDT has been extended to include systemic delivery as well as topical application of photosensitizers. The model has been tested for its capability to mimic an animal tumor model and to serve for PDT studies by measuring drug fluorescence and PDT-induced effects. Three second-genera tion photosensitizers have been tested for their ability to produce photody namic response in the chick embryo/CAM system when delivered by IP injectio n: 5-aminolevulinic acid (ALA), benzoporphyrin derivative monoacid ring A ( BPD-MA), and Lutetium-texaphyrin (Lu-Tex). Exposure of the CAM vasculature to the appropriate laser light results in light-dose-dependent vascular dam age with all three compounds. Localization of ALA following IP injections i n embryos, whose CAMs have been implanted with rat ovarian cancer cells to produce nodules, is determined in real time by fluorescence of the photoact ive metabolite protoporphyrin IX (PpIX). Dose-dependent fluorescence in the normal CAM vasculature and the tumor implants confirms the uptake of ALA f rom the peritoneum, systemic circulation of the drug, and its conversion to PpIX. (C) 1999 Elsevier Science S.A. All rights reserved.