Pharmacokinetics of 5-aminolevulinic-acid-induced porphyrins in tumour-bearing mice

Abstract

Photodynamic therapy and photodynamic diagnosis help to support efficient treatment of superficial and early-stage cancer. During the last few years, 5-aminolevulinic acid (5-ALA), a precursor of haemoglobin in the haem biosynthetic pathway, was used to stimulate endogenous porphyrin production. In the following the time dependence of 5-ALA-induced porphyrin concentration will be investigated on several tissues in an indashvivo tumour model. 5-ALA was administered intravenously at a concentration of 50 mg kg −1 body weight. According to a certain time schedule the animals were sacrificed and 12 different organs as well as the tumour were removed. During excitation with the violet light of a Kr + laser, porphyrin fluorescence spectra in the range 550–750 nm could be detected on the tissue samples. The intensity of the emission spectra at λ = 635±2 nm was taken as a measure of the porphyrin concentration. All tissues showed porphyrin fluorescence. Brightest fluorescence was found on the tumour. A maximum contrast of the flourescence intensity between the tumour and the nondashmalignant organs of up to 30 was observed at 4–6 h post-injection. The kinetics of the porphyrin concentration depend on the organ. Simple mathematical models will be derived and discussed.