5-aminolevulinic-acid-hexyl-ester and hypericin

In flat bladder cancer and carcinoma in situ, and in multifocal papillary cancer, some smaller lesions may be overlooked at cystoscopy. For 10 years fluorescence cystoscopy has been promoted to solve these problems without wider acceptance. New fluorophobes now promise better clinical applicability.. In prospective multicenter studies fluorescence cystoscopy shows significant improvement in the detection of flat bladder cancer and carcinoma in situ. It also permits more reliable identification of all neoplastic lesions with multifocal tumors, hence more precise removal and as a consequence lower recurrence rates.. New agents bring a significant benefit. Hexyl-aminolevulinate offers more rapid urothelial accumulation, better fluorescence contrast and less photobleaching than previously used fluorophobes. It is simple to use in everyday practice and has a favorable toxicity profile.

Topics: Aminolevulinic Acid; Anthracenes; Carcinoma in Situ; Cystoscopy; Fluorescence; Fluorescent Dyes; Humans; Perylene; Practice Guidelines as Topic; Predictive Value of Tests; Sensitivity and Specificity; Urinary Bladder Neoplasms

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.

Topics: Aminolevulinic Acid; Animals; Anthracenes; Antineoplastic Agents; Female; Fluorescence; Perylene; Photochemotherapy; Povidone; Protoporphyrins; Rats; Rats, Inbred F344; Solubility; Tissue Distribution; Urinary Bladder Neoplasms