The possibility of using the
porphyrin precursor 5-aminolevulinic
acid to cause selective
porphyrin accumulation in
tumors was examined. Syngeneic colon
carcinomas CC531 were implanted in the livers of Wag/Rij rats. Groups of three to six animals each were given 2 mg/mL of 5-aminolevulinic
acid in
drinking water from the 8th, 14th, or 17th day after
tumor implantation. Two other groups received either 2.5 or 5 mg/kg of
Photofrin II (Photomedica Inc., Raritan, NJ) intravenously on day 17. On day 19 the livers were removed and
porphyrin concentrations were measured in normal livers and
tumors by
solvent extraction and high-performance liquid chromatography.
Protoporphyrin accumulated progressively in
tumors with increasing duration of 5-aminolevulinic
acid administration (P = 0.0001), whereas no increase was found in normal livers. After 11 days of 5-aminolevulinic
acid administration the
porphyrin concentration ratio between
tumors and livers was 4:1. In contrast, after
Photofrin II administration the concentration was higher in normal livers than in
tumors (1:3 ratio,
tumor to liver).
Enzyme measurements showed a threefold decrease in
ferrochelatase activity in
tumors compared with livers (P less than 0.001). In conclusion,
oral administration of 5-aminolevulinic
acid results in progressive accumulation of
protoporphyrin in a transplantable colon
carcinoma without accumulation in the surrounding liver tissue. This selective accumulation of
porphyrins appears to be caused by a relative
ferrochelatase deficiency in malignant tissue. 5-Aminolevulinic
acid administration may be a suitable approach to photosensitizing liver
tumors for
photodynamic therapy or to early detection of
tumors by fluorescence in ultraviolet light.