אסיף מאגר המחקר החקלאי

Mechanism and relevance to photodynamic therapy of chloroaluminum sulfonated phthalocyanine tissue distribution in dogs

Year:

1990

Source of publication :

Authors :

Volume :

3

Co-Authors:

Ben-Hur, E., Department of Radiochemistry, Nuclear Research Center - Negev, P.O. Box 9001, Beer-Sheva 84190, Israel
Zuk, M.M., Department of Radiochemistry, Nuclear Research Center - Negev, P.O. Box 9001, Beer-Sheva 84190, Israel
Orenstein, A., Department of Radiochemistry, Nuclear Research Center - Negev, P.O. Box 9001, Beer-Sheva 84190, Israel
Rosenthal, I., Department of Radiochemistry, Nuclear Research Center - Negev, P.O. Box 9001, Beer-Sheva 84190, Israel
Crane, S.W., Department of Radiochemistry, Nuclear Research Center - Negev, P.O. Box 9001, Beer-Sheva 84190, Israel

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Abstract:

Phthalocyanines are second-generation photosensitizers that are being developed for photodynamic therapy. Chloroaluminum phthalocyanine tetrasulfonate (AIPCS) was administered i.v. to normal dogs and its levels were determined in tissues using a sensitive HPLC assay. AIPCS accumulated in high levels in liver, spleen, bone marrow, kidney and lung, confirming previous studies in mice and rats. Low levels of AIPCS were detected in skin, and this may explain the low cutaneous phototoxicity. AIPCS was barely detectable in muscles, cornea and brain and it was cleared from the circulation within 24 h, primarily via the kidneys, clearance being faster in males than in females. There were also statistically significant tissue distribution differences between the genders, particularly during the first 12 h. This difference is not only intriguing but suggests that the optimal time window for treatment may vary by gender. Using cultured endothelial cells the question of how AIPCS in serum is distributed to the tissues was addressed. The kinetics of depletion of AIPCS from serum incubated with endothelial cells was followed for up to 24 h and t( 1/2 ) was found to exceed 24 h considerably. Since maximal AIPCS levels in most tissues were obtained during the first 12 h after administration, it is suggested that passage of AIPCS from serum to tissues occurs primarily through the openings beween endothelial cells and not via uptake of the dye by the latter. Light exposure of a highly vascular tissue (chicken comb) indicated that maximal response occurred 1 h after AIPCS administration. Since photodynamic effects are mediated primarily by blood vessels occlusion, the optimal time window for this effect should be verified for various tissue sites.

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