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Photodynamic therapy (PDT) continues to evolve into a mature clinical treatment of a variety of cancer types as well as
age-related macular degeneration of the eye. However, there are still aspects of PDT that need to be improved in order
for greater clinical acceptance. While a number of new PDT photo-sensitizers, sometimes referred to as second- or third-
generation therapeutic agents, are currently under clinical investigation, the direct treatment through the skin of
subcutaneous tumors deeper than 5 mm remains problematic. Currently approved PDT porphyrin photo-sensitizers, as
well as several modified porphyrins (e.g. chlorins, bacteriochlorins, etc.) that are under clinical investigation can be
activated at 630-730 nm, but none above 800 nm. It would be highly desirable if new PDT paradigms could be
developed that would allow photo-activation deep in the tissue transparency window in the Near-infrared (NIR) above
800 nm to reduce scattering and absorption phenomena that reduce deep tissue PDT efficacy. Rasiris and MPA
Technologies have developed new porphyrins that have greatly enhanced two-photon absorption ( P A ) cross-sections
and can be activated deep in the NIR (ca. 780-850 nm). These porphyrins can be incorporated into a therapeutic triad that
also employs an small molecule targeting agent that directs the triad to over-expressed tumor receptor sites, and a NIR
onephoton imaging agent that allows tracking the delivery of the triad to the tumor site, as well as clearance of excess
triad from healthy tissue prior to the start of PDT treatment. We are currently using these new triads in efficacy studies
with a breast cancer cell line that has been transfected with luciferase genes that allow implanted tumor growth and post-
PDT treatment efficacy studies in SCID mouse models by following the rise and decay of the bioluminescence signal.
We have also designed highly absorbing and scattering collagen breast cancer phantoms in which we have demonstrated
dramatic cell kill to a depth of at least 4 cm. We have also demonstrated that at the wavelength and laser fluences used in
the treatment of implanted tumors in the mouse mammary fat pads, there is little, if any, damage to the skin or internal
mouse organs. In addition, we have also demonstrated that the implanted tumors can be treated to a depth of more than 1
cm by direct radiation through the dorsal side of the mouse.
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