Effects of fractionated 5-aminolevulinic acid administration on tissue levels of protoporphyrin in vivo.
The photodynamic therapy (PDT) of malignant tissues can be achieved via the administration of 5-aminolevulinic acid (ALA), which is naturally converted to the photoreactive substance protoporphyrin IX (PP). This study compares bolus with fractionated ALA dosing in order to determine whether one of these methods results in a higher tissue concentration of PP. Mice bearing a subcutaneously implanted colon-26 tumor were treated with ALA (200 mg kg-1), given intravenously either as a single bolus or as three equally divided doses at 50 min intervals. Tissue samples of tumor, kidney, skin, liver, skeletal muscle, colon and plasma were obtained 2, 3, 4 and 6 h later for the analysis of PP concentrations. Fractionated dosing results in significantly higher concentrations of PP at 4 and 6 h for kidney, 3 and 6 h for skin, 3 h for colon and 6 h for liver. In contrast, fractionated dosing has no significant effect on the PP concentrations of muscle and plasma. Fractionated dosing results in a significantly greater PP concentration in the tumor 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 fractionated dosing may not cause a significant increase in the PP concentration in colon-26 tumors relative to that observed for the bolus dose.
Herman
M A
MA
Department of Surgery, Wayne State University, Detroit, MI 48201, USA.
Webber
J
J
Luo
Y
Y
Patacsil
V
V
Kessel
D
D
Fromm
D
D
D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D051379:Mice; D017319:Photosensitizing Agents / Q000378:metabolism*; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011524:Protoporphyrins / Q000378:metabolism*
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX