IN-VIVO FLUORESCENCE KINETICS AND LOCALIZATION OF ALUMINUM PHTHALOCYANINE DISULFONATE IN AN AUTOLOGOUS TUMOR-MODEL

Sulphonated phthalocyanines are studied as photosensitisers for photod ynamic therapy of cancer. Their strong fluorescence and tumour-localis ing properties make them also potentially useful for detection of canc er by fluorescence. For this purpose, we have studied the fluorescence kinetics and localisation of aluminium phthalocyanine disulphonate (A IPcS(2)) in 4-nitroquinoline 1-oxide (4NQO)-induced dysplasia and inva sive cancer of the oral mucosa of the hard palate in Wistar albino rat s. Twenty-two rats were divided into six groups. Five groups were subj ected to a 4NQO application period of 8, 12, 16, 20 or 26 weeks and on e was a control group. The dysplasia varied from slight to severe and was correlated with the duration of the application period. All animal s received a dose of 1 mu mol kg(-1) ALPcS(2) i.v. Fluorescence images were recorded via a specially designed 'palatoscope' with excitation at 460 +/- 20 nm for autofluorescence, 610 +/- 15 nm for AlPcS(2) fluo rescence and detection of emission at 675 +/- 15 nm. After subtraction of the two images the specific AlPcS(2) fluorescence remained. AlPcS( 2)-mediated fluorescence increased significantly when the severity of dysplasia increased (P<0.04). also the phenomenon of strong fluorescen t spots on the fluorescence images was observed. This always occurred within the first 10 h after injection of ALPcS(2). Histological analys is showed a local alteration to the mucosa in 67% of these spots, whic h was either invasive cancer (29%) or inflammation (38%). These result s suggest two different mechanisms of AlPcS(2) uptake in tissue, one a ssociated with the presence of generalised dysplasia and another assoc iated with local changes of the epithelial/connective tissue, which is not necessarily specific for tumours.