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Proceedings Paper

Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic
Author(s): Edward V. Maytin; Sanjay Anand; Christine Baran; Golara Honari; Sara Lohser; Angela Kyei; Philip Bailin; Brian W. Pogue
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Paper Abstract

Nonmelanoma skin carcinomas are the most common of all human cancers. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) has been used to treat these tumors, but has shown variable results. We are pursuing a multifaceted approach toward optimizing tumor responsiveness. First, a new paradigm is being developed in which tumors are pretreated with differentiation-inducing agents, e.g. methotrexate or Vitamin D, to enhance synthesis of protoporphyrin IX (PpIX) and improve tumor cell killing upon exposure to 635 nm light. This principle was first elucidated in cell culture studies, and has now been shown to hold true for murine skin tumors, and for a human subcutaneous tumor model (A431 cells injected in nude mice). Clinical trials to test methotrexate and Vitamin D as augmenting agents for ALA-PDT of nonmelanoma skin cancer are being designed. Second, better methods to measure PpIX in patients' skin tumors in real time are being developed. In a clinical study to measure PpIX in patients with dysplastic skin lesions, in vivo fluorescence dosimetry was used to measure the accumulation of PpIX over time, and revealed that intralesional PpIX may reach clinically-useful levels earlier than previously thought for the treatment of actinic keratoses. In a second clinical study to examine depth of PpIX production in nonmelanoma skin cancer, the depth of PpIX within BCC tumors was found at relatively deep levels (>1 mm) in some tumor nests, but not in others. Production of PpIX in deep squamous cell carcinoma was very low. In summary, molecular approaches such as differentiation therapy to enhance ALA-PDT for individual patients may ultimately be needed to help to improve skin cancer responses to this modality.

Paper Details

Date Published: 24 February 2009
PDF: 9 pages
Proc. SPIE 7164, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVIII, 71640K (24 February 2009); doi: 10.1117/12.808174
Show Author Affiliations
Edward V. Maytin, Lerner Research Institute, Cleveland Clinic (United States)
Sanjay Anand, Lerner Research Institute, Cleveland Clinic (United States)
Christine Baran, Lerner Research Institute, Cleveland Clinic (United States)
Golara Honari, Lerner Research Institute, Cleveland Clinic (United States)
Sara Lohser, Lerner Research Institute, Cleveland Clinic (United States)
Angela Kyei, Lerner Research Institute, Cleveland Clinic (United States)
Philip Bailin, Lerner Research Institute, Cleveland Clinic (United States)
Brian W. Pogue, Dartmouth Medical School (United States)


Published in SPIE Proceedings Vol. 7164:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVIII
David H. Kessel, Editor(s)

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