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Title: Elucidation of the tumoritropic principle of hypericin
Authors: Van de Putte, Marie
Roskams, Tania
Vandenheede, Jackie
Agostinis, Patrizia
de Witte, Peter # ×
Issue Date: Apr-2005
Publisher: Harcourt Publishers
Series Title: British Journal of Cancer vol:92 issue:8 pages:1406-13
Abstract: Hypericin is a potent agent in the photodynamic therapy of cancers. To better understand its tumoritropic behaviour, we evaluated the major determinants of the accumulation and dispersion of hypericin in subcutaneously growing mouse tumours. A rapid exponential decay in tumour accumulation of hypericin as a function of tumour weight was observed for each of the six tumour models investigated, and a similar relationship was found between tumour blood flow and tumour weight. Moreover, there was a close correlation between the higher hypericin uptake in RIF-1 tumours compared to R1 tumours and tumour vessel permeability. To define the role of lipoproteins in the transport of hypericin through the interstitial space, we performed a visual and quantitative analysis of the colocalization of hypericin and DiOC18-labelled lipoproteins in microscopic fluorescent overlay images. A coupled dynamic behaviour was found early after injection (normalised fluorescence intensity differences were on the whole less than 10%), while a shifted pattern in localisation of hypericin and DiOC18 was seen after 24 h, suggesting that during its migration through the tumour mass, hypericin is released from the lipoprotein complex. In conclusion, we were able to show that the tumour accumulation of hypericin is critically determined by a combination of biological (blood flow, vessel permeability) and physicochemical elements (affinity for interstitial constituents).
URI: 
ISSN: 0007-0920
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Pharmaceutical Biology (-)
Translational Cell & Tissue Research
Biochemistry Section (Medicine) (-)
Laboratory of Cell Death Research & Therapy
× corresponding author
# (joint) last author

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