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Proceedings Paper

Targeted two-photon photodynamic therapy for the treatment of subcutaneous tumors
Author(s): Charles W. Spangler; Jean R. Starkey; Fanqing Meng; Aijun Gong; Mikhail Drobizhev; Aleksander Rebane; B. Moss
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Paper Abstract

Photodynamic therapy (PDT) has developed into a mature technology over the past several years, and is currently being exploited for the treatment of a variety of cancerous tumors, and more recently for age-related wet macular degeneration of the eye. However, there are still some unresolved problems with PDT that are retarding a more general acceptance in clinical settings, and thus, for the most part, the treatment of most cancerous rumors still involves some combination of invasive surgery, chemotherapy and radiation treatment, particularly subcutaneous tumors. Currently approved PDT agents are activated in the Visible portion of the spectrum below 700 nm, Laser light in this spectral region cannot penetrate the skin more than a few millimeters, and it would be more desirable if PDT could be initiated deep in the Near-infrared (NIR) in the tissue transparency window (700-1000 nm). MPA Technologies, Inc. and Rasiris, Inc. have been co-developing new porphyrin PDT designed to have greatly enhanced intrinsic two-photon cross-sections (>800 GM units) whose two-photon absorption maxima lie deep in the tissue transparency window (ca. 780-850 nm), and have solubility characteristics that would allow for direct IV injection into animal models. Classical PDT also suffers from the lengthy time necessary for accumulation at the tumor site, a relative lack of discrimination between healthy and diseased tissue, particularly at the tumor margins, and difficulty in clearing from the system in a reasonable amount of time post-PDT. We have recently discovered a new design paradigm for the delivery of our two-photon activated PDT agents by incorporating the porphyrins into a triad ensemble that includes a small molecule targeting agent that directs the triad to over-expressed tumor receptor sites, and a NIR one-photon imaging agent that allows the tracking of the triad in terms of accumulation and clearance rates. We are currently using these new two-photon PDT triads in efficacy studies with two breast cancer cell lines, both in vitro and in vivo. Both of these cell lines have been transfected with luciferase genes that allow implanted tumor growth and PDT efficacy to be monitored in living mouse models over time by following the rise and decay of the bioluminescence signals.

Paper Details

Date Published: 8 April 2005
PDF: 8 pages
Proc. SPIE 5689, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIV, (8 April 2005); doi: 10.1117/12.589210
Show Author Affiliations
Charles W. Spangler, MPA Technologies, Inc. (United States)
Jean R. Starkey, Montana State Univ. (United States)
Fanqing Meng, MPA Technologies, Inc. (United States)
Aijun Gong, MPA Technologies, Inc. (United States)
Mikhail Drobizhev, Montana State Univ./Bozeman (United States)
Aleksander Rebane, Montana State Univ./Bozeman (United States)
B. Moss, Montana State Univ./Bozeman (United States)

Published in SPIE Proceedings Vol. 5689:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIV
David Kessel, Editor(s)

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