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Noninvasive Molecular Imaging of MYC mRNA Expression in Human Breast Cancer Xenografts with a [99mTc]Peptide−Peptide Nucleic Acid−Peptide Chimera

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Departments of Biochemistry and Molecular Pharmacology, Radiology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and Department of Surgery, University of Missouri, Columbia, Missouri 65212
Cite this: Bioconjugate Chem. 2005, 16, 1, 70–79
Publication Date (Web):December 31, 2004
https://doi.org/10.1021/bc0497923
Copyright © 2005 American Chemical Society

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    Abstract

    Human estrogen receptor-positive breast cancer cells typically display elevated levels of Myc protein due to overexpression of MYC mRNA, and elevated insulin-like growth factor 1 receptor (IGF1R) due to overexpression of IGF1R mRNA. We hypothesized that scintigraphic detection of MYC peptide nucleic acid (PNA) probes with an IGF1 peptide loop on the C-terminus, and a [99mTc]chelator peptide on the N-terminus, could measure levels of MYC mRNA noninvasively in human IGF1R-overexpressing MCF7 breast cancer xenografts in nude mice. We prepared the chelator-MYC PNA-IGF1 peptide, as well as a 4-nt mismatch PNA control, by solid-phase synthesis. We imaged MCF7 xenografts scintigraphically and measured the distribution of [99mTc]probes by scintillation counting of dissected tissues. MCF7 xenografts in nude mice were visualized at 4 and 24 h after tail vein administration of the [99mTc]PNA probe specific for MYC mRNA, but not with the mismatch control. The [99mTc]probes distributed normally to the kidneys, livers, tumors, and other tissues. Molecular imaging of oncogene mRNAs in solid tumors with radiolabel-PNA−peptide chimeras might provide additional genetic characterization of preinvasive and invasive breast cancers.

     Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University.

     Department of Radiology, Thomas Jefferson University.

     University of Missouri.

    §

     Kimmel Cancer Center, Thomas Jefferson University.

    *

     Corresponding author:  Dr. Eric Wickstrom, Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, 219 Bluemle Life Sciences Building, 233 S. 10th St., Philadelphia PA 19107-5541, voice:  215-955-4578, fax:  215-955-4580 or 215-923-9214, [email protected], website:  http://tesla.jci.tju.edu.

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