title: Fluorescence pharmacokinetics of Lutetium Texaphyrin (PCI-0123, Lu-Tex) in the skin and in healthy and tumoral hamster cheek-pouch mucosa.
abstract: We have investigated the pharmacokinetics (PK) of Lutetium Texaphyrin (Lu-Tex), a second-generation photosensitizer, in the Syrian hamster cheek pouch early cancer model. Ten male hamsters, five with chemically induced early squamous cell cancer of the left cheek pouch, received an intracardiac injection of a 10 mg/ml Lu-Tex solution, resulting in a dose of 12 mg Lu-Tex per kg of bodyweight. The PK of the dye have been measured during the 24 h following the injection with an optical-fiber-based spectrofluorometer on the ventral skin, the healthy and the tumoral cheek-pouch mucosa. The Lu-Tex fluorescence is excited at 460 nm and detected around 740 nm. All the measurements yield very similar pharmacokinetic curves. The fluorescence intensity reaches a maximum between two and three hours after the injection and, at its maximum, it is consistently higher (up to 1.5 times) on the tumor than on the healthy mucosa. It remains smaller on the skin than on cheek-pouch mucosa. After 24 h, the Lu-Tex fluorescence is no longer detectable either on the skin, on the lesion or on the healthy mucosa. Moreover, Lu-Tex clearly displays a significant fluorescence selectivity between early carcinoma and healthy mucosa in this model. Furthermore, the inter-animal fluctuations of the fluorescence signal are small (+/-16% on the tumor-bearing mucosa). Eight-minute-long skin-irradiation tests have been performed 24 h after the injection of the Lu-Tex on the ventral skin of 16 additional animals with a solar simulator. No reaction is observed, either macroscopically or microscopically, which further demonstrates, as suggested by the fluorescence measurements, that this photosensitizer is significantly cleared from the skin after 24 h.
authors.affiliation: Institute of Environmental Engineering, DGR-LPAS, EPFL, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Zellweger
authors.forename: A
authors.initials: A
authors.lastname: Radu
authors.forename: P
authors.initials: P
authors.lastname: Monnier
authors.forename: H
authors.initials: H
authors.lastname: van den Bergh
authors.forename: G
authors.initials: G
authors.lastname: Wagnières
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002278:Carcinoma in Situ / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D008665:Metalloporphyrins / Q000493:pharmacokinetics*; D008856:Microscopy, Fluorescence / Q000379:methods; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D013472:Sunlight
chemical_list: D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C102825:motexafin lutetium; D015127:9,10-Dimethyl-1,2-benzanthracene; C437683:motexafin gadolinium