EFFECTS OF FRACTIONATED 5-AMINOLEVULINIC ACID ADMINISTRATION ON TISSUE-LEVELS OF PROTOPORPHYRIN IN-VIVO

The photodynamic therapy (PDT) of malignant tissues can be achieved vi a the administration of 5-aminolevulinic acid (ALA), which is naturall y converted to the photoreactive substance protoporphyrin IX (PP). Thi s study compares bolus with fractionated ALA dosing in order to determ ine whether one of these methods results in a higher tissue concentrat ion of PP. Mice bearing a subcutaneously implanted colon-26 tumor were treated with ALA (200 mg kg(-1)), given intravenously either as a sin gle bolus or as three equally divided doses at 50 min intervals. Tissu e samples of tumor, kidney, skin, liver, skeletal muscle, colon and pl asma were obtained 2, 3, 4 and 6 h later for the analysis of PP concen trations. Fractionated dosing results in significantly higher concentr ations of PP at 4 and 6 h for kidney, 3 and 6 h for skin, 3 h for colo n and 6 h for liver. In contrast, fractionated dosing has no significa nt effect on the PP concentrations of muscle and plasma. Fractionated dosing results in a significantly greater PP concentration in the tumo r at 3 h relative to that observed for the bolus dose. However, from a consideration of the time of PP measurement, it is concluded that fra ctionated dosing may not cause a significant increase in the PP concen tration in colon-26 tumors relative to that observed for the bolus dos e. (C) 1997 Published by Elsevier Science S.A.