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

• Published in: Urologic oncology 2002-05, Vol.7 (3), p.125-132
• Main Authors: Xiao, Zhengwen, Tamimi, Yahya, Brown, Kevin, Tulip, John, Moore, Ronald
• Format: Article
• Language: English
• Subjects: 5-aminolevulinic acid; Adenocarcinoma - diagnostic imaging; Adenocarcinoma - drug therapy; Aminolevulinic Acid - therapeutic use; Animals; Interstitial photodynamic therapy; Male; Photochemotherapy; Photosensitizing Agents - therapeutic use; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - drug therapy; Protoporphyrin IX; Radionuclide Imaging; Rats; Rats, Inbred F344; Transitional cell carcinoma; Tumor Cells, Cultured; Urinary Bladder Neoplasms - diagnostic imaging; Urinary Bladder Neoplasms - drug therapy
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/S1078-1439(01)00184-3

Photodynamic therapy (PDT) may be an attractive option for treatment of early stage prostate cancer. Aminolevulinic acid (ALA) acts as a pro-drug leading to a selective accumulation of a photosensitizer, protoporphyrin IX (PpIX), in epithelial 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 ∼1000 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 99mTc-HMPAO scintigraphy to evaluate tumor perfusion changes 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 4× 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 4× treatment volume was 13.7 days in the control group, 179.3, 183.3, 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). 99mTc-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.