title: Patched targeting peptides for imaging and treatment of hedgehog positive breast tumors.
abstract: High tumor hedgehog expression is correlated with poor prognosis in invasive ductal carcinoma. Peptides which bind the patched receptor have recently been reported to have a growth inhibitory effect in tumors with activated hedgehog signaling. We sought to examine growth inhibition with these peptides in breast cancer cells and use these peptides as molecular imaging probes to follow changes in hedgehog expression after chemotherapy. Significant growth inhibition was observed in breast cancer cell lines treated with PTCH-blocking peptides. Significant in vitro uptake was observed with both FITC- and (99m)Tc-EC-peptide conjugates. In vivo imaging studies displayed greater accumulation of (99m)Tc-labeled peptides within tumors as compared to adjacent muscle tissue. Patched receptor expression increased after treatment and this correlated with an increase in tumor radiotracer uptake. These studies suggest that peptides which bind the sonic hedgehog docking site in patched receptor correlate with patched expression and can be used to image patched in vivo. Further, our data suggest that radiolabeled peptides may enable us to examine the activity of the hedgehog signaling pathway and to evaluate response to anti-cancer therapies.
authors.affiliation: Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Smith
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Fanlin
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Richard
authors.identifier: 0000-0003-1301-931X
authors.initials: R
authors.lastname: Larson
authors.affiliation: Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute, Christiana Care Health System, 4701 Ogletown-Stanton Road, Newark, DE 19713, USA.
authors.forename: Jennifer
authors.identifier: 0000-0003-1602-4560
authors.initials: J
authors.lastname: Sims-Mourtada
authors.affiliation: Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives; D003952:Diagnostic Imaging; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology; D013194:Staining and Labeling; D013667:Technetium; D023041:Xenograft Model Antitumor Assays
chemical_list: D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010455:Peptides; C000606239:Ptch1 protein, rat; D011956:Receptors, Cell Surface; C109063:ethylene dicysteine; D013667:Technetium; D003545:Cysteine