EVIDENCE FOR DIFFERENT MECHANISMS OF EMT-6 TUMOR NECROSIS BY PHOTODYNAMIC THERAPY WITH DISULFONATED ALUMINUM PHTHALOCYANINE OR PHOTOFRIN - TUMOR-CELL SURVIVAL AND BLOOD-FLOW
Ws. Chan et al., EVIDENCE FOR DIFFERENT MECHANISMS OF EMT-6 TUMOR NECROSIS BY PHOTODYNAMIC THERAPY WITH DISULFONATED ALUMINUM PHTHALOCYANINE OR PHOTOFRIN - TUMOR-CELL SURVIVAL AND BLOOD-FLOW, Anticancer research, 16(4A), 1996, pp. 1887-1892
A comparison was made of photodynamic therapy (PDT) mediated by two ph
otosensitizers, the disulfonated aluminium phthalocyanine (AlPcS(2)) a
nd Photofrin(circle) (PII) with regard to their mechanism of action on
murine tumours. Balb/c mice bearing intradermally growing EMT-6 tumor
s were injected intravenously with either 1 mu mol kg(-1) body weight
of AlPcS(2) 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 AlPcS(2) and 600-650 nm,
400 J cm(-2) for PII. Tumor cell survival following in vivo PDT was d
etermined by an in vitro clonogenicity assay on the dissociated tumors
. Immediately after the completion of light irradiation, a reduction o
f similar to 72% in the number of clonogenic cells was seen with AlPcS
(2)-treated tumor versus similar to 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 indire
ct PDT action, however, the decline in cell viability was steeper in t
he first 6 h with PII-PDT than with AlPcS(2)-PDT. 24 h after PDT, the
clonogenic capacity of both AlPcS(2)- and PII-PDT treated tumor fell t
o similar to 3% of the control tumor. The PDT effect on tumor blood fl
ow as a measure of the tumor vascular damage was monitored by the rete
ntion of Tc-99m-MIBI in the tumor. Little effect on tumor blood flow w
as seen with AlPcS(2)-PDT at 0 h after the completion of light treatme
nt. Thereafter the blood flow declined slowly and remained at similar
to 50% the level of the control by 24 h post-PDT. In contrast, PII pro
voked a similar to 40% reduction of tumor blood flow immediately after
the completion of photo irradiation, which then fell to similar to 20
% within 2 h and similar to 7% by 24 h post-PDT. These results indicat
e the involvement of both direct and indirect mechanisms in the PDT in
duced tumor necrosis. However, AlPcS(2)-PDT exerted a larger direct tu
mor cell phototoxic effect, whereas PII-PDT induced tumor cell death t
o a greater extent via an indirect effect that parallels the extensive
damage to the tumor vasculature.