Abstract
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 using intraperitoneal (IP) photosensitizer injection of the chick embryo, use 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-generation photosensitizers have been tested for their ability to produce photodynamic response in the chick embryo/CAM system when delivered by IP injection: 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 damage with all three compounds. Localization of ALA following IP injections in embryos, whose CAMs have been implanted with rat ovarian cancer cells to produce nodules, is determined in real time by fluorescence of the photoactive metabolite protoporphyrin IX (PpIX). Dose-dependent fluorescence in the normal CAM vasculature and the tumor implants confirms the uptake of ALA from the peritoneum, systemic circulation of the drug, and its conversion to PpIX.
Highlights
Photodynamic therapy (PDT) dependson the differential uptake and retention of light-sensitive compoundsin tumor tissue.Exposureto therapeuticlight, at awavelength selected to coincide with an absorption peak of the photosensitizer, resultsin oxidation-mediateddestruction of the tumor mass and its supporting vasculature with minimal damageto the surrounding normal tissues [ 141
The aims of this study were two-fold: ( 1) to demonstrate the feasibility and usefulness of systemic photosensitizer administration to the chorioallantoic membrane (CAM) model for PDT studies by showing that the CAM vasculature is a photodynamic target of the circulating photosensitizer; (2) to demonstrate the feasibility of using IP injected chick embryos and their CAM systems for LIFD studies by measuring the localization of a fluorescent compound over time in an implanted tumor
Cell implantation of the CAM is technically possible by EDD 5 [41], we found that EDD 8 provided the optimal conditions
Summary
Photodynamic therapy (PDT) dependson the differential uptake and retention of light-sensitive compoundsin tumor tissue.Exposureto therapeuticlight, at awavelength selected to coincide with an absorption peak of the photosensitizer, resultsin oxidation-mediateddestruction of the tumor mass and its supporting vasculature with minimal damageto the surrounding normal tissues [ 141. ’ Permanent address: Department of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel. Animal models, such as rodents [ 13-351, rabbits [36], dogs [ 37,381, andprimates [ 39,401have beenusedin PDT andLIFD experiments.Specializedskinfold chamberseven makeit possibleto visualize directly smalltumors andtheir surrounding vasculature during experimentation [ 19,201. The chick embryo chorioallantoic membrane(CAM) model usesthe well-vascularized chorioallantoic membrane of fertilized chicken eggsand presentsan attractive in vivo model. It is inexpensive, allowsdirect visualization andvideo documentation of blood vessels,is easy to handle, and statistically useful numbersare attainablerelatively quickly. Despitethe easeof visualization of the tumors and their vascularization when grown on the CAM, the model hasbeenusedmainly to study PDTinduced injury of normalCAM vessels[ 46-491 andlessfor
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