Light dose fractionation to enhance photodynamic therapy using 5-aminolevulinic acid in the normal rat colon

5-Aminolevulinic acid (ALA) is an attractive photosensitizing agent for pho todynamic therapy (PDT) as its photoactive derivative, protoporphyrin IX, i s metabolized within 1-2 days, eliminating prolonged skin photosensitivity. However, at the maximum dose patients can tolerate by mouth, 60 mg/kg, onl y superficial effects are seen. This paper extends earlier studies on enhan cing the effect by light fractionation, Experiments in the normal rat colon looked at the area of necrosis around a single light delivery fiber 3 days after PDT with a range of light-dose fractionation regimes, All animals we re given 200 mg/kg ALA intravenously 2 h prior to light delivery (100 mW at 635 nm) and each interruption in illumination was for 150 s, The area of P DT necrosis (total dose 25 J) could be increased by a factor of 3 with a si ngle interval after 5 J, compared with continuous illumination. Alternative ly, with this single break, the total light dose could be reduced by 60% to achieve the same area of necrosis as with continuous illumination. This si mple modification to PDT with ALA could markedly reduce current treatment t imes as well as increasing clinical efficacy.