Preclinical evaluation of a novel water-soluble chlorin E6 derivative (BLC 1010) as photosensitizer for the closure of the neovessels.
In the present study, photodynamic activity of a novel photosensitizer (PS), Chlorin e(6)-2.5 N-methyl-d-glucamine (BLC 1010), was evaluated using the chorioallantoic membrane (CAM) as an in vivo model. After intravenous (i.v.) injection of BLC 1010 into the CAM vasculature, the applicability of this drug for photodynamic therapy (PDT) was assessed in terms of fluorescence pharmacokinetics, i.e. leakage from the CAM vessels, and photothrombic activity. The influence of different PDT parameters including drug and light doses on the photodynamic activity of BLC 1010 has been investigated. It was found that, irrespective of drug dose, an identical continuous decrease in fluorescence contrast between the drug inside and outside the blood vessels was observed. The optimal treatment conditions leading to desired vascular damage were obtained by varying drug and light doses. Indeed, observable damage was achieved when irradiation was performed at light doses up to 5 J/cm(2) 1 min after i.v. injection of drug doses up to 0.5 mg/kg body weight(b.w.). However, when irradiation with light doses of more than 10 J/cm(2) was performed 1 min after injection of drug doses up to 2 mg/kg body weight, this led to occlusion of large blood vessels. It has been demonstrated that it is possible to obtain the desired vascular occlusion and stasis with BLC 1010 for different combinations of drug and/or light doses.
Pegaz
B
B
Ecole Polytechnique Fédérale de Lausanne, EPFL-ENAC-LPAS, Station 6, CH-1015 Lausanne, Suisse.
Debefve
E
E
Borle
F
F
Ballini
J-P
JP
Wagnières
G
G
Spaniol
S
S
Albrecht
V
V
Scheglmann
D
D
Nifantiev
N E
NE
van den Bergh
H
H
Konan
Y N
YN
D000818:Animals; D002196:Capillaries / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D002642:Chick Embryo; D002735:Chlorophyllides; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects* / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004353:Drug Evaluation, Preclinical; D008027:Light; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D014867:Water / Q000737:chemistry
D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water; C062985:phytochlorin