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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 639562, 8 pages
http://dx.doi.org/10.1155/2012/639562
Research Article

Detection of Canonical Hedgehog Signaling in Breast Cancer by 131-Iodine-Labeled Derivatives of the Sonic Hedgehog Protein

1Helen F. Graham Cancer Center, Christiana Care Hospital, Newark, DE 19713, USA
2RadioMedix, Inc., Houston, TX 77042, USA
3Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 70030, USA
5Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA

Received 29 February 2012; Revised 23 April 2012; Accepted 7 May 2012

Academic Editor: Lie-Hang Shen

Copyright © 2012 Jennifer Sims-Mourtada et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Activation of hedgehog (HH) pathway signaling is observed in many tumors. Due to a feedback loop, the HH receptor Patched (PTCH-1) is overexpressed in tumors with activated HH signaling. Therefore, we sought to radiolabel the PTCH-1 ligand sonic (SHH) for detection of cancer cells with canonical HH activity. Receptor binding of 131I-SHH was increased in cell lines with high HH pathway activation. Our findings also show that PTCH-1 receptor expression is decreased upon treatment with HH signaling inhibitors, and receptor binding of 131I-SHH is significantly decreased following treatment with cyclopamine. In vivo imaging and biodistribution studies revealed significant accumulation of 131I-SHH within tumor tissue as compared to normal organs. Tumor-to-muscle ratios were approximately 8 : 1 at 5 hours, while tumor to blood and tumor to bone were 2 : 1 and 5 : 1, respectively. Significant uptake was also observed in liver and gastrointestinal tissue. These studies show that 131I-SHH is capable of in vivo detection of breast tumors with high HH signaling. We further demonstrate that the hedgehog receptor PTCH-1 is downregulated upon treatment with hedgehog inhibitors. Our data suggests that radiolabeled SHH derivatives may provide a method to determine response to SHH-targeted therapies.