title: In vivo fluorescence kinetics and localisation of aluminum phthalocyanine disulphonate in an autologous tumour model.
abstract: Sulphonated phthalocyanines are studied as photosensitizers for photodynamic therapy of cancer. Their strong fluorescence and tumour-localising properties make them also potentially useful for detection of cancer by fluorescence. For this purpose, we have studied the fluorescence kinetics and localisation of aluminum phthalocyanine disulphonate (AlPcS2) in 4-nitroquinoline 1-oxide (4NQO)-induced dysplasia and invasive cancer of the oral mucosa of the hard palate in Wistar albino rats. Twenty-two rats were divided into six groups. Five groups were subjected to a 4NQO application period of 8, 12, 16, 20 or 26 weeks and one was a control group. The dysplasia varied from slight to severe and was correlated with the duration of the application period. All animals received a dose of 1 micromol/kg AlPcS2 i.v. Fluorescence images were recorded via a specially designed 'palatoscope' with excitation at 460 +/- 20 nm for autofluorescence, 610 +/- 15 nm for AlPcS2 fluorescence and detection of emission at 675 +/- 15 nm. After subtraction of the two images the specific AlPcS2 fluorescence remained. AlPcS2-mediated fluorescence increased significantly when the severity of dysplasia increased (P<0.04). Also the phenomenon of strong fluorescent spots on the fluorescence images was observed. This always occurred within the first 10 h after injection of AlPcS2. Histological analysis showed a local alteration to a mucosa in 67% of these spots, which was either invasive cancer (29%) or inflammation (38%). These results suggest two different mechanisms of AlPcS2 uptake in tissue, one associated with the presence of generalised dysplasia and another associated with local changes of the epithelial/connective tissue, which is not necessarily specific for tumours.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital, Groningen, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Witjes
authors.forename: O C
authors.initials: OC
authors.lastname: Speelman
authors.forename: P G
authors.initials: PG
authors.lastname: Nikkels
authors.forename: C A
authors.initials: CA
authors.lastname: Nooren
authors.forename: J M
authors.initials: JM
authors.lastname: Nauta
authors.forename: B
authors.initials: B
authors.lastname: van der Holt
authors.forename: H L
authors.initials: HL
authors.lastname: van Leengoed
authors.forename: W M
authors.initials: WM
authors.lastname: Star
authors.forename: J L
authors.initials: JL
authors.lastname: Roodenburg
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism*; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D007211:Indoles / Q000032:analysis / Q000493:pharmacokinetics*; D009942:Organometallic Compounds / Q000032:analysis / Q000493:pharmacokinetics*; D010157:Palatal Neoplasms / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005456:Fluorescent Dyes; D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; D015112:4-Nitroquinoline-1-oxide; C064331:aluminum phthalocyanine disulfonate