PHOTOSENSITIZATION OF MURINE TUMOR, VASCULATURE AND SKIN BY 5-AMINOLEVULINIC ACID-INDUCED PORPHYRIN

The effects of topical and systemic administration of 5-aminolevulinic acid (ALA) were examined in several murine tumor systems with regard to porphyrin accumulation kinetics in tumor, skin and blood, vascular and tumor cell photosensitization and tumor response after light expos ure. Marked, transient increases in porphyrin levels were observed in tumor and skin after systemic and topical ALA. Rapid, transient, dose- dependent porphyrin increases were also observed in blood; these were pronounced after systemic ALA injection and mild after topical applica tion. They were highest within 1 h after ALA injection, thereafter dec lining rapidly. This matched the clearing kinetics of injected exogeno us protoporphyrin IX (PpIX). initially, vascular photosensitivity chan ged inversely to blood porphyrin levels, increasing gradually up to 5 h post-ALA, as porphyrin was clearing from the bloodstream. This patte rn was again matched by injected, exogenous PpIX. After therapeutic tu mor treatment vascular disruption of the tumor bed, while observed, wa s incomplete, especially at the tumor base. Minimal direct tumor cell kill was found at low photodynamic therapy (PDT) doses (250 mg/kg ALA, 135 J/cm(2) light). Significant, but limited (<1 log) direct photodyn amic tumor cell kill was obtained when the PDT dose was raised to 500 mg/kg systemic ALA, followed 3 h later by 270 J/cm(2), a dose that was however toxic to the animals. The further reduction of clonogenic tum or cells over 24 h following treatment was moderate and probably limit ed by the incomplete disruption of the vasculature. Tumor responses we re highest when light treatment was carried out at the time of highest tumor porphyrin content rather than at the time of highest vascular p hotosensitivity. Tumor destruction did not reach the tumor base, regar dless of treatment conditions.