TUMOR-LOCALIZATION KINETICS OF PHOTOFRIN AND 3 SYNTHETIC PROPHYRINOIDS IN AN AMELANOTIC MELANOMA OF THE HAMSTER

In this study the localisation of porphyrinoid photosensitisers in tum ours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitisers, int ravital fluorescence microscopy and chemical extraction were used. Ame lanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Sy rian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of ti ssue and blood samples was performed to verify and supplement intravit al microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the differe nt porphycenes was found to be highly tumour selective (3.2:1), anti-t umour selective (0.2:1), and non-selective (1:1) with increasing polar ity of the porphycenes. The two non-tumour selective porphycenes had d istinctly- accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly dist ributed, tumour selective photosensitisers, occurred exclusively durin g the distribution from serum and uptake into tissues. For the most se lective porphycene. the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accu mulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be at tributed to an enhanced uptake rate for lipophilic molecules in this s ubcutaneously growing neoplasm. The slow distribution of the two tumou r specific photosensitisers and the strong fluorescence of these hydro phobic molecules in the tumour compartment with a high water content i ndicate a carrier role of serum proteins in the selection process. Enh anced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these tw o sensitisers.