title: Exploration of the mechanism underlying the tumor necrosis avidity of hypericin.
abstract: Hypericin, a potent necrosis avid agent, features a peculiar affinity for necrotic tissue. Necrosis avid contrast agents have been investigated as markers for non-invasive imaging of different disorders. In view of the promising clinical applications, a more complete knowledge of the mechanism of action is important for the future development of new chemical structures with improved characteristics. To study whether a compound-specific or non-specific mechanism based on plasma lipoprotein transport is involved in the accumulation of hypericin in intratumoral necrosis, we performed a visual and quantitative fluoromicroscopic analysis of the colocalization of hypericin and DiOC18-labeled lipoproteins in subcutaneous murine radiation-induced fibrosarcoma tumors. Microscopic fluorescent overlay images of necrotic tumors demonstrated that hypericin already showed clear necrosis avid characteristics 4 h after injection, whereas a similar outstanding accumulation in necrosis was not demonstrated for the labeled lipoproteins. Moreover, a quantitative analysis of fluoromicroscopic images of tumor necrosis at 24 h after injection showed differences in normalized fluorescence intensities between hypericin and labeled lipoproteins of 50-100%, reflecting a shifted pattern in localization. We conclude that our results are indicative of a release of hypericin from the lipoprotein complex at some point along its way through the peri-necrotic tumor area and the necrotic tissue debris, which is in line with the hypothesis of a compound-specific mechanism.
authors: Laboratory for Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, 3000 Leuven, Belgium.
authors: Marie
authors: M
authors: Van de Putte
authors: Yicheng
authors: Y
authors: Ni
authors: Peter A M
authors: PA
authors: De Witte
mesh_terms: D000818:Animals; D000873:Anthracenes; D002232:Carbocyanines / Q000378:metabolism; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009336:Necrosis; D010569:Perylene / Q000031:analogs & derivatives* / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000473:pathology*; D044004:Xanthones / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D002232:Carbocyanines; D008074:Lipoproteins; D044004:Xanthones; C066668:vadimezan; D010569:Perylene; C098044:3,3'-dioctadecyloxacarbocyanine; C004965:hypericin