Bw. Henderson et al., PHOTOSENSITIZATION OF MURINE TUMOR, VASCULATURE AND SKIN BY 5-AMINOLEVULINIC ACID-INDUCED PORPHYRIN, Photochemistry and photobiology, 62(4), 1995, pp. 780-789
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.