PurposeIn this preclinical study we examined the biodistribution of hypericin formulated as its watersoluble 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).
MethodsFreshly 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.
ResultsThe results of these experiments show that PVP-hypericin (30 µM) accumulated about 3.5-fold more in malignant urothelial tissue as compared to normal urothelium, whereas PpIX accumulated to the same extent in malignant and normal urothelium, both after intra-bladder 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 to 8.3 for 16 and 8 mM HAL, respectively.
ConclusionsThis 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.