A comparison was made of
photodynamic therapy (
PDT) mediated by two
photosensitizers, the
disulfonated aluminum phthalocyanine (
AlPcS2) and
Photofrin* (PII) with regard to their mechanism of action on murine
tumors. Balb/c mice bearing intradermally growing EMT-6
tumors were injected intravenously with either 1 mumol kg-1
body weight of
AlPcS2 or 5 mg/kg of PII 24 h prior to red light irradiation from a
Xenon lamp (650-700 nm, 200 mW cm-2, for
AlPcS2 and 600-650 nm, 400 J cm-2 for PII.
Tumor cell survival following in vivo
PDT was determined by an in vitro clonogenicity assay on the dissociated
tumors. Immediately after the completion of light irradiation, a reduction of approximately 72% in the number of clonogenic cells was seen with
AlPcS2-treated
tumor versus approximately 24% of that for PII-treated
tumor. Further loss of clonogenic cell survival progressed as a function of time following
PDT, and was considered to be the consequence of indirect
PDT action, however, the decline in cell viability was steeper in the first 6 h with PII-
PDT than with
AlPcS2-
PDT. 24 h after
PDT, the clonogenic capacity of both
AlPcS2-and PII-
PDT treated
tumor fell to approximately 3% of the control
tumor. The
PDT effect on
tumor blood flow as a measure of the
tumor vascular damage was monitored by the retention of 99mTc-MIBI in the
tumor. Little effect on
tumor blood flow was seen with
AlPcS2-
PDT at 0 h after the completion of light treatment. Thereafter the blood flow declined slowly and remained at approximately 50% the level of the control by 24 h post-
PDT. In contrast, PII provoked a approximately 40% reduction of
tumor blood flow immediately after the completion of photo irradiation, which then fell to approximately 20% within 2 h and approximately 7% by 24 h post-
PDT. These results indicate the involvement of both direct and indirect mechanisms in the
PDT induced
tumor necrosis. However,
AlPcS2-
PDT exerted a larger direct
tumor cell phototoxic effect, whereas PII-
PDT induced
tumor cell death to a greater extent via an indirect effect that parallels the extensive damage to the
tumor vasculature.