Biodistribution of PVP-hypericin and hexaminolevulinate-induced PpIX in normal and orthotopic tumor-bearing rat urinary bladder
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In this preclinical study, we examined the biodistribution of hypericin formulated as its water-soluble PVP-hypericin complex in the different layers (urothelium, submucosa, muscle) of a normal rat bladder and a rat bladder bearing a malignant urothelium composed of syngeneic AY-27 tumor cells. The results were compared with the biodistribution of hexaminolevulinate (HAL)-induced protoporphyrin IX (PpIX).
Freshly prepared PVP-hypericin and HAL solutions were instilled in both normal as well as tumor-bearing rat bladders. Following instillation, bladders were removed and snap frozen in liquid nitrogen. Fluorescence of PVP-hypericin or PpIX-induced HAL was measured in the bladder layers and quantified using image analysis software.
The results of these experiments show that PVP-hypericin (30 μM) accumulated about 3.5-fold more in malignant urothelial tissue when compared to normal urothelium, whereas PpIX accumulated to the same extent in malignant and normal urothelium, both after intrabladder instillation of 8 or 16 mM HAL. Besides, PVP-hypericin and PpIX accumulated selectively in the urothelium with a tumor-to-muscle ratio of 30.6 for PVP-hypericin and 3.7–8.3 for 16 and 8 mM HAL, respectively.
This study shows that PVP-hypericin appears to have great potential as a photodynamic agent against non-muscle-invasive bladder cancers after intravesical administration, with a limited risk of affecting the deeper layers of the bladder.
KeywordsBladder cancer Orthotopic animal model PVP-hypericin HAL
Hematoxylin and eosin
Non-muscle-invasive bladder cancer
This work was supported by grants awarded by Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (F.W.O-Vlaanderen), by the K.U.Leuven (onderzoekstoelage) and by Sanochemia Pharmazeutika AG (Austria).
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