Enhancement of tumor responsiveness to aminolevulinate-photodynamic therapy (ALA-PDT) using differentiation-promoting agents in mouse models of skin carcinoma

Sanjay Anand; Golara Honari; Akshat Paliwal; Tayyaba Hasan; Edward V. Maytin

doi:10.1117/12.822972

13 July 2009 Enhancement of tumor responsiveness to aminolevulinate-photodynamic therapy (ALA-PDT) using differentiation-promoting agents in mouse models of skin carcinoma

Sanjay Anand, Golara Honari, Akshat Paliwal, Tayyaba Hasan, Edward V. Maytin

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Proceedings Volume 7380, Photodynamic Therapy: Back to the Future; 73804B (2009) https://doi.org/10.1117/12.822972
Event: 12th World Congress of the International Photodynamic Association, 2009, Seattle, Washington, United States

Abstract

Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is an emerging treatment for cancers. ALA, given as a prodrug, selectively accumulates and is metabolized in cancer cells to form protoporphyrin IX (PpIX). Targeted local irradiation with light induces cell death. Since the efficacy of ALA-PDT for large or deep tumors is currently limited, we are developing a new approach that combines differentiation-inducing agents with ALA-PDT to improve the clinical response. Here, we tested this new combination paradigm in the following two models of skin carcinoma in mice: 1) tumors generated by topical application of chemical carcinogens (DMBA-TPA); 2) human SCC cells (A431) implanted subcutaneously. To achieve a differentiated state of the tumors, pretreatment with a low concentration of methotrexate (MTX) or Vitamin D (Vit D) was administered for 72 h prior to exposure to ALA. Confocal images of histological sections were captured and digitally analyzed to determine relative PpIX levels. PpIX in the tumors was also monitored by real-time in vivo fluorescence dosimetry. In both models, a significant increase in levels of PpIX was observed following pretreatment with MTX or Vit D, as compared to no-pretreatment controls. This enhancing effect was observed at very low, non-cytotoxic concentrations, and was highly specific to cancer cells as compared to normal cells. These results suggest that use of differentiating agents such as MTX or Vit D, as a short-term combination therapy given prior to ALA-PDT, can increase the production of PpIX photosensitizer and enhance the therapeutic response of skin cancers.

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Sanjay Anand, Golara Honari, Akshat Paliwal, Tayyaba Hasan, and Edward V. Maytin "Enhancement of tumor responsiveness to aminolevulinate-photodynamic therapy (ALA-PDT) using differentiation-promoting agents in mouse models of skin carcinoma", Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 73804B (13 July 2009); https://doi.org/10.1117/12.822972

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