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Use of Halogenated
Xanthenes to Specifically Target Diseased Tissue
Dees, Craig1,
Harkins, Jay1, Scott, Timmothy1
and Wachter, Eric1
Photogen, Inc.1
Abstract-
Cancer treatments frequently require surgical intervention and may include
radiation, chemotherapy or both. The adverse side effects accompanying
therapy include disfigurement, loss of organ function, general or specific
suppression of immune system competence, pain and debilitation. The
use of photodynamic therapy (PDT) to treat cancer may improve efficacy
and reduce effects on normal tissue. We compared the efficacy of a number
of halogenated (HX) proprietary photosensitizers with that of several
conventional PDT agents using Staphylococcus aureus and Eschericia coli.
The ability of HX agents to kill bacteria was superior to that demonstrated
by porphyrin-based PDT agents. Chemically modified HX agents were also
evaluated for their propensity to specifcally target tumor tissue. Modified
HX agents were selectively retained in subcutaneous melanomas, hepatomas,
breast and renal adenocarcinomas following intratumoral injection. Moreover,
orally delivered HX exhibited preferential concentraton into subcutaneous
tumors in mice. Illumination of tumors implanted on the left flank of
mice eliminated the tumors. Illuminaton of normal tissue around the
tumor or on the right flank of mice produced slight erythema in a few
mice. The effects in normal tissue were similar to that produced by
the illumination alone. No evidence of pain, discomfort or inflamation
outside the area occupied by the tumor was observed in any animal even
if very large tumors were treated with HX PDT. Animals cured of tumors
using HX PDT were challenged by attempting to introduce a second tumor
in the mice. In all cases it proved impossible to introduce a second
tumor into the mice even at 3 months post-treatment. The use of HX PDT
to treat neoplastic disease effectively confines the effects of treatment
to diseased tissue, reduces or eliminates undersirable side effects
while simultaneously stimulating long lasting antitumor immunity.
Keywords: photodynamic
, antitumor, immunity, cancer
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