Systemic application of photosensitizers in the chick chorioallantoic membrane (CAM) model: photodynamic response of CAM vessels and 5-aminolevulinic acid 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 using intraperitoneal (i.p.) 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 i.p. 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 i.p. 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.
Hornung
R
R
Beckman Laser Institute and Medical Clinic, University of California, Irvine, USA.
Hammer-Wilson
M J
MJ
Kimel
S
S
Liaw
L H
LH
Tadir
Y
Y
Berns
M W
MW
D000482:Allantois / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007700:Kinetics; D008665:Metalloporphyrins / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D008665:Metalloporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; C102825:motexafin lutetium; C504224:benzoporphyrin D; C437683:motexafin gadolinium; D000622:Aminolevulinic Acid