ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

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

View Author Information
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
Copyright © 2005 American Chemical Society

    Article Views





    Read OnlinePDF (367 KB)


    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:

    Cited By

    This article is cited by 35 publications.

    1. Nariman V. Amirkhanov, Kaijun Zhang, Mohan R. Aruva, Mathew L. Thakur and Eric Wickstrom . Imaging Human Pancreatic Cancer Xenografts by Targeting Mutant KRAS2 mRNA with [111In]DOTAn-Poly(diamidopropanoyl)m-KRAS2 PNA-d(Cys-Ser-Lys-Cys) Nanoparticles. Bioconjugate Chemistry 2010, 21 (4) , 731-740.
    2. Xiankai Sun,, Huafeng Fang,, Xiaoxu Li,, Raffaella Rossin,, Michael J. Welch, and, John-Stephen Taylor. MicroPET Imaging of MCF-7 Tumors in Mice via unr mRNA-Targeted Peptide Nucleic Acids. Bioconjugate Chemistry 2005, 16 (2) , 294-305.
    3. Jingping Geng, Xuan Xia, Lin Teng, Lidan Wang, Linlin Chen, Xiangli Guo, Bonn Belingon, Jason Li, Xuemei Feng, Xianghui Li, Wendou Shang, Yingying Wan, Hu Wang. Emerging landscape of cell-penetrating peptide-mediated nucleic acid delivery and their utility in imaging, gene-editing, and RNA-sequencing. Journal of Controlled Release 2022, 341 , 166-183.
    4. Yaqun Jiang, Yongkang Gai, Yu Long, Qingyao Liu, Chunbao Liu, Yongxue Zhang, Xiaoli Lan. Application and Evaluation of [ 99m Tc]-Labeled Peptide Nucleic Acid Targeting MicroRNA-155 in Breast Cancer Imaging. Molecular Imaging 2020, 19 , 153601212091612.
    5. Hyung Tae Lee, Se Kye Kim, Jang Won Yoon. Antisense peptide nucleic acids as a potential anti-infective agent. Journal of Microbiology 2019, 57 (6) , 423-430.
    6. Eric Wickstrom. DNA and RNA derivatives to optimize distribution and delivery. Advanced Drug Delivery Reviews 2015, 87 , 25-34.
    7. Marybeth A. Pysz, Jürgen K. Willmann. Applications of Molecular Small-Animal Imaging in Oncology. 2014, 585-636.
    8. Holger Stephan, Christian Foerster, Gilles Gasser. Synthesis, Characterization, and Evaluation of Radiometal-Containing Peptide Nucleic Acids. 2014, 37-54.
    9. Bishnuhari Paudyal, Kaijun Zhang, Chang-Po Chen, Matthew E. Wampole, Neil Mehta, Edith P. Mitchell, Brian D. Gray, Jeffrey A. Mattis, Koon Y. Pak, Mathew L. Thakur, Eric Wickstrom. Determining efficacy of breast cancer therapy by PET imaging of HER2 mRNA. Nuclear Medicine and Biology 2013, 40 (8) , 994-999.
    10. R. Alberto, H. Braband. SPECT/PET Imaging with Technetium, Gallium, Copper, and Other Metallic Radionuclides. 2013, 785-817.
    11. Qingqing Meng, Zheng Li. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer. International Journal of Biomedical Imaging 2013, 2013 , 1-14.
    12. Gilles Gasser, Anna M. Sosniak, Nils Metzler-Nolte. Metal-containing peptide nucleic acid conjugates. Dalton Transactions 2011, 40 (27) , 7061.
    13. Gilles Gasser, Anna M. Sosniak, Anna Leonidova, Henrik Braband, Nils Metzler-Nolte. Towards the Preparation of Novel Re/99mTc Tricarbonyl-Containing Peptide Nucleic Acid Bioconjugates. Australian Journal of Chemistry 2011, 64 (3) , 265.
    14. Gilles Gasser, Katrin Jäger, Martin Zenker, Ralf Bergmann, Jörg Steinbach, Holger Stephan, Nils Metzler-Nolte. Preparation, 99mTc-labeling and biodistribution studies of a PNA oligomer containing a new ligand derivative of 2,2′-dipicolylamine. Journal of Inorganic Biochemistry 2010, 104 (11) , 1133-1140.
    15. Peng Fu, Baozhong Shen, Changjiu Zhao, Guomei Tian. Molecular Imaging of MDM2 Messenger RNA with 99m Tc-Labeled Antisense Oligonucleotides in Experimental Human Breast Cancer Xenografts. Journal of Nuclear Medicine 2010, 51 (11) , 1805-1812.
    16. Fanny Marlin, Philippe Simon, Tula Saison‐Behmoaras, Carine Giovannangeli. Delivery of Oligonucleotides and Analogues: The Oligonucleotide Conjugate‐Based Approach. ChemBioChem 2010, 11 (11) , 1493-1500.
    17. Armin W. Opitz, Eric Wickstrom, Mathew L. Thakur, Norman J. Wagner. Physiologically Based Pharmacokinetics of Molecular Imaging Nanoparticles for mRNA Detection Determined in Tumor-Bearing Mice. Oligonucleotides 2010, 20 (3) , 117-125.
    18. Rajendra Joshi, Ritu Mishra, Rolf Pohmann, Jörn Engelmann. MR contrast agent composed of cholesterol and peptide nucleic acids: Design, synthesis and cellular uptake. Bioorganic & Medicinal Chemistry Letters 2010, 20 (7) , 2238-2241.
    19. Eric Wickstrom, Mathew L. Thakur. Genetic and Molecular Approaches to Imaging Breast Cancer. 2010, 163-182.
    20. Mathew L. Thakur. Genomic Biomarkers for Molecular Imaging: Predicting the Future. Seminars in Nuclear Medicine 2009, 39 (4) , 236-246.
    21. Archana Mukherjee, Eric Wickstrom, Mathew L. Thakur. Imaging oncogene expression. European Journal of Radiology 2009, 70 (2) , 265-273.
    22. Nariman V. Amirkhanov, Ivan Dimitrov, Armin W. Opitz, Kaijun Zhang, John P. Lackey, Christopher A. Cardi, Song Lai, Norman J. Wagner, Mathew L. Thakur, Eric Wickstrom. Design of (Gd‐DO3A) n ‐polydiamidopropanoyl‐peptide nucleic acid‐ D (Cys‐Ser‐Lys‐Cys) magnetic resonance contrast agents. Biopolymers 2008, 89 (12) , 1061-1076.
    23. Catarina Xavier, Clelia Giannini, Lurdes Gano, Stefano Maiorana, Roger Alberto, Isabel Santos. Synthesis, characterization, and evaluation of a novel 99mTc(CO)3 pyrazolyl conjugate of a peptide nucleic acid sequence. JBIC Journal of Biological Inorganic Chemistry 2008, 13 (8) , 1335-1344.
    24. R. Juliano, Md. R. Alam, V. Dixit, H. Kang. Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides. Nucleic Acids Research 2008, 36 (12) , 4158-4171.
    25. Md Rowshon Alam, Vidula Dixit, Hyunmin Kang, Zi-Bo Li, Xiaoyuan Chen, JoAnn Trejo, Michael Fisher, Rudy L. Juliano. Intracellular delivery of an anionic antisense oligonucleotide via receptor-mediated endocytosis. Nucleic Acids Research 2008, 36 (8) , 2764-2776.
    26. Fang Jia, Said Daibes Figueroa, Fabio Gallazzi, Baghavathy S. Balaji, Mark Hannink, Susan Z. Lever, Timothy J. Hoffman, Michael R. Lewis. Molecular Imaging of bcl-2 Expression in Small Lymphocytic Lymphoma Using 111 In-Labeled PNA–Peptide Conjugates. Journal of Nuclear Medicine 2008, 49 (3) , 430-438.
    27. Suzanne A. Eccles, Lenaic Paon. Models for Breast Cancers. 2007
    28. Antony K. Chen, Mark A. Behlke, Andrew Tsourkas. Avoiding false-positive signals with nuclease-vulnerable molecular beacons in single living cells. Nucleic Acids Research 2007, 35 (16) , e105.
    29. W. Su, R. Mishra, J. Pfeuffer, K.‐H. Wiesmüller, K. Ugurbil, J. Engelmann. Synthesis and cellular uptake of a MR contrast agent coupled to an antisense peptide nucleic acid – cell– penetrating peptide conjugate. Contrast Media & Molecular Imaging 2007, 2 (1) , 42-49.
    30. André A. Neves, Kevin M. Brindle. Assessing responses to cancer therapy using molecular imaging. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2006, 1766 (2) , 242-261.
    31. Robin L. Kilker, Maricarmen D. Planas-Silva. Cyclin D1 Is Necessary for Tamoxifen-Induced Cell Cycle Progression in Human Breast Cancer Cells. Cancer Research 2006, 66 (23) , 11478-11484.
    32. Girja S Shukla, David N Krag. Selective delivery of therapeutic agents for the diagnosis and treatment of cancer. Expert Opinion on Biological Therapy 2006, 6 (1) , 39-54.
    33. XIAOBING TIAN, ATIS CHAKRABARTI, NARIMAN V. AMIRKHANOV, MOHAN R. ARUVA, KAIJUN ZHANG, BOBY MATHEW, CHRISTOPHER CARDI, WENYI QIN, EDWARD R. SAUTER, MATHEW L. THAKUR, ERIC WICKSTROM. External Imaging of CCND1 , MYC , and KRAS Oncogene mRNAs with Tumor‐Targeted Radionuclide‐PNA‐Peptide Chimeras. Annals of the New York Academy of Sciences 2005, 1059 (1) , 106-144.
    34. Igor G. Panyutin, Ronald D. Neumann. The potential for gene-targeted radiation therapy of cancers. Trends in Biotechnology 2005, 23 (10) , 492-496.
    35. Wafik S. El-Deiry. Meeting Report: The International Conference on Tumor Progression and Therapeutic Resistance. Cancer Research 2005, 65 (11) , 4475-4484.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Your Mendeley pairing has expired. Please reconnect