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Biodistribution of PVP-hypericin and hexaminolevulinate-induced PpIX in normal and orthotopic tumor-bearing rat urinary bladder

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Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

PVP:

Polyvinylpyrrolidone

HAL:

Hexaminolevulinate

PpIX:

Protoporphyrin IX

DiO:

3,3′-Dioctadecyloxacarbocyanine perchlorate

H&E:

Hematoxylin and eosin

NMIBC:

Non-muscle-invasive bladder cancer

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Acknowledgments

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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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Laboratory for Pharmaceutical Biology, Katholieke Universiteit Leuven, Herestraat 49, Bus 824, 3000, Leuven, Belgium

    Joachim Vandepitte & Peter A. M. de Witte

  2. Department of Urology, University Hospital Leuven, 3000, Leuven, Belgium

    Ben Van Cleynenbreugel & Hendrik Van Poppel

  3. Sanochemia Pharmazeutika AG, 1090, Vienna, Austria

    Klaudia Hettinger

Authors
  1. Joachim Vandepitte
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  2. Ben Van Cleynenbreugel
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  3. Klaudia Hettinger
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  4. Hendrik Van Poppel
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  5. Peter A. M. de Witte
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Correspondence to Peter A. M. de Witte.

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Vandepitte, J., Van Cleynenbreugel, B., Hettinger, K. et al. Biodistribution of PVP-hypericin and hexaminolevulinate-induced PpIX in normal and orthotopic tumor-bearing rat urinary bladder. Cancer Chemother Pharmacol 67, 775–781 (2011). https://doi.org/10.1007/s00280-010-1375-0

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