UPTAKE AND KINETICS OF C-14-LABELED META-TETRAHYDROXYPHENYLCHLORIN AND 5-AMINOLEVULINIC ACID IN THE C6 RAT GLIOMA MODEL

Meta-tetrahydroxyphenylchlorin (m-THPC) and 5-aminolaevulinic acid (5- ALA) are two second-generation photosensitizers which are currently un der investigation for photodynamic therapy (PDT) and photodynamic diag nosis (PDD). So far, the experience with these photosensitizers for us e within brain tumours is limited. We examined the distribution and re tention of C-14-labelled m-THPC and [C-14]5-ALA in the rat C6 glioma b rain tumour model. After intraperitoneal injection of m-THPC (71 909 d .p.m. mu l(-1); 0.16 mg ml(-1) m-THPC; 0.3 mg kg(-1)), the following a ctivities were found after 36 h: brain tumour 223 664 d.p.m. g(-1), br ain contralateral to the tumour side 2567 d.p.m. g(-1), liver 369 959 d.p.m. g(-1) and skin 55 197 d.p.m. g(-1); 100 000 d.p.m. correspondin g to 0.22 mu g of m-THPC. After 7 days, the concentration of m-THPC de creased to 76 277 d.p.m. g(-1) in tumour and 635 d.p.m. g(-1) in brain . The radioactivity after intravenous administration of [C-14]5-ALA (2 3 079 d.p.m, mu l(-1); 40 mg ml(-1); 120 mg kg(-1)) increased within 1 5 min (59 634 d.p.m. g(-1) in tumour, 17 427 d.p.m. g(-1) in brain); a fter 8 h only a small amount (3653 d.p.m, g(-1) in tumour) remained. B rain adjacent to the tumour was also found to have a higher uptake of 5-ALA. This study provides basic information for the use of m-THPC and 5-ALA in brain tumours. Because of the different pharmacokinetic and toxicological profile, we recommend m-THPC for PDT and 5-ALA for PDD. Clinical trials now have to prove the superior phototoxic properties o f these second-generation photosensitizers.