Interstitial photodynamic therapy in subcutaneously implanted urologic tumors in rats after intravenous administration of 5-aminolevulinic acid

Photodynamic therapy (PDT) may be an attractive option for treatment of early stage prostate cancer. Aminolevulinic acid (ALA) acts as a prodrug leading to a selective accumulation of a photosensitizer, protoporphyrin IX (PpIX), in epithelia] cells. We investigated the efficacy of ALA-mediated PDT for rat R3327-H prostate cancer, compared with the AY-27 bladder tumor. Rats bearing either AY-27 or R3327-H tumors were randomized to different groups when their tumors reached similar to1000 mm(3). At the day of PDT, animals were administered 500 mg/kg ALA intravenously 4 hours prior to laser therapy. The argon-pumped dye laser light (630 nm) was coupled to multiple quartz fibers with cylindrical diffusing tips,, which were inserted into the tumor in icosahedral pattern. Light exposure was varied to yield doses of 1000 to 3000 J/tumor. Animals bearing R3327-H tumors were imaged with Tc-99m-HMPAO scintigraphy to evaluate tumor perfusion chances induced by PDT. There was a light-dose dependent tumor response in both tumor models. The mean time for R3327-H tumor to re-grow to 4x treatment volume was 79.7 days in the control group (light only), 159 days in 1000 J group, and 169 days in 2000 J group (P < 0.05). Tumors treated with 3000 J were clinically cured (P < 0.01), Likewise, for AY-27 tumors, the average time to re-grow to 4x treatment volume was 13.7 days in the control group, 179.3, 1833, and 185,7 days in groups of 1000, 1500. and 2000 J (P < 0.05), respectively, Tumors treated with 3000 J were clinically cured (P < 0.01). Tc-99m-HMPAO scintigraphy demonstrated a mild perfusion impairment following PDT. Interstitial PDT with ALA/PpIX is equally effective in treating prostate cancer and TCC in these heterotopic rat models. (C) 2002 Elsevier Science, Inc. All rights reserved.