Biodistribution of PVP-hypericin and hexaminolevulinate-induced PpIX in normal and orthotopic tumor-bearing rat urinary bladder.
OBJECTIVE
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.
Vandepitte
Joachim
J
Faculty of Pharmaceutical Sciences, Laboratory for Pharmaceutical Biology, Katholieke Universiteit Leuven, Herestraat 49, Bus 824, 3000 Leuven, Belgium.
Van Cleynenbreugel
Ben
B
Hettinger
Klaudia
K
Van Poppel
Hendrik
H
de Witte
Peter A M
PA
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D005453:Fluorescence; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010778:Photochemotherapy / Q000379:methods; D011205:Povidone / Q000737:chemistry*; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility; D014018:Tissue Distribution; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D000873:Anthracenes; D000970:Antineoplastic Agents; D011524:Protoporphyrins; D010569:Perylene; C004965:hypericin; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D011205:Povidone; C419924:5-aminolevulinic acid hexyl ester