Share Email Print

Proceedings Paper

Enhancement of tumor responsiveness to aminolevulinate-photodynamic therapy (ALA-PDT) using differentiation-promoting agents in mouse models of skin carcinoma
Author(s): Sanjay Anand; Golara Honari; Akshat Paliwal; Tayyaba Hasan; Edward V. Maytin
Format Member Price Non-Member Price
PDF $17.00 $21.00

Paper 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.

Paper Details

Date Published: 13 July 2009
PDF: 7 pages
Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 73804B (13 July 2009); doi: 10.1117/12.822972
Show Author Affiliations
Sanjay Anand, Cleveland Clinic (United States)
Golara Honari, Cleveland Clinic (United States)
Akshat Paliwal, Cleveland Clinic (United States)
Tayyaba Hasan, Wellman Ctr. for Photomedicine. MGH (United States)
Harvard Medical School (United States)
Edward V. Maytin, Cleveland Clinic (United States)
Wellman Ctr. for Photomedicine, MGH (United States)
Harvard Medical School (United States)

Published in SPIE Proceedings Vol. 7380:
Photodynamic Therapy: Back to the Future
David H. Kessel, Editor(s)

© SPIE. Terms of Use
Back to Top
Sign in to read the full article
Create a free SPIE account to get access to
premium articles and original research
Forgot your username?