Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75-minute interval

We have studied different single and fractionated illumination schemes afte r systemic administration of 5-aminolevulinic acid (ALA) to improve the res ponse of nodular tumors to ALA-mediated photodynamic therapy. Tumors transp lanted on the thigh of female WAG/Rij rats were transdermally illuminated w ith red light (633 nm) after systemic ALA administration (200 mg/kg), The e ffectiveness of each treatment scheme was determined from the tumor volume doubling time. A single illumination (100 J/cm(2) at 100 mW/cm(2), 2.5 h af ter ALA administration) yielded a doubling time of 6.6 +/- 1.2 days. This w as significantly different from the untreated control (doubling time, 1.7 /- 0.1 days). The only treatment scheme that yielded a significant improvem ent compared to all other schemes studied was illumination at both 1 and 2. 5 h after ALA administration (both 100 J/cm(2) at 100 mW/cm(2)) and resulte d in a tumor volume doubling time of 18.9 +/- 2.9 days. A possible mechanis m to explain this phenomenon is that the protoporphyrin IX formed after adm inistration of ALA is photodegraded by the first illumination, In the 75-mi n interval, new porphyrin is termed enhancing the effect of the second illu mination.