Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster.
In this study the localisation of porphyrinoid photosensitizers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitizers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitizers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitizers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers.
Leunig
M
M
Institute for Surgical Research, Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Munich, Germany.
Richert
C
C
Gamarra
F
F
Lumper
W
W
Vogel
E
E
Jocham
D
D
Goetz
A E
AE
D000818:Animals; D001692:Biological Transport; D006224:Cricetinae; D017323:Dihematoporphyrin Ether / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism*; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013997:Time Factors
D017319:Photosensitizing Agents; D011166:Porphyrins; D017323:Dihematoporphyrin Ether