Investigative Urology

Abstract

5-Aminolevulinic acid (ALA) is a precursor of heme biosynthesis. In the penultimate step of this biosynthesis, protoporphyrin IX (PpIX), an effective photosensitizer, is generated. In this study, the biodistribution and photodynamic effect of ALA-induced PpIX were investigated in an orthotopic rat bladder tumor model. A quantitative comparison of PpIX biodistribution by extraction and fluorescence spectroscopy following intravenous and intravesical administration of ALA was made. The tumor to normal bladder wall ratio was 2:1 at 4 hours for both delivery modes. Fluorescence microscopy demonstrated predominantly cellular rather than stromal PpIX fluorescence. Phototoxicity, evaluated 4 hours after ALA administration, was light dose-dependent with the most efficient tumor necrosis being observed upon 150 J/cm.2 of 630 nm. irradiation. These data suggest that optimized photodynamic therapy with ALA-induced PpIX may be an alternative treatment for superficial bladder carcinoma.

Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization

“…Regardless of the mechanism, a time delay of 1-4 h following administration of ALA is generally required for localization of PpIX in the target tissue prior to imaging (or treatment). The specific time delay depends on the route of delivery (intravenous, oral, intravesical instillation, topical, or inhalation) and the tissue in question, [51][52][53][54] with PpIX levels dependent upon the cellular differentiation status. 55 Other studies described below reveal that, for certain applications, the hexyl and/or methyl ester derivatives of ALA (HAL and MAL, respectively, Figure 7) result in similar PpIX production but with improved penetration and more homogeneous distribution in malignant tissue as discussed below.…”

Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer

“…Several investigations were conducted in order to optimize these parameters in a rat Barrett’s esophagus model [ 97 , 98 , 99 ]. The kinetics and spectra of ALA-induced fluorescence were determined in tumor and surrounding tissue of amelanotic melanoma in hamsters [ 100 ], various mammary carcinoma bearing mice [ 19 , 20 ], superficial bladder carcinoma in rats [ 101 ], human hepatocellular carcinoma cell [ 102 ], human nasopharyngeal carcinoma and human rectal cancer in nude mice [ 103 , 104 ]. Prolonged animal survival followed by photodynamic therapy using ALA was reported by several groups in various experimental models.…”

Ultrasound-Guided Intramural Inoculation of Orthotopic Bladder Cancer Xenografts: A Novel High-Precision Approach

“…Alternative models include the inoculation of murine bladder cancer cells in immunocompetent mice (syngeneic model) [11] as well as transgenic models [12]. Similar models are also possible in rats [13], [14].…”