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Genetic and Molecular Approaches to Imaging Breast Cancer

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Breast Cancer Risk Reduction and Early Detection

Abstract

Imaging gene expression non-invasively, with high sensitivity and specificity, would provide a more powerful diagnostic tool than any currently available. Although CT, MRI, and ultrasound have made great strides, none of the current modalities can image oncogene expression directly. No other reliable method is currently available to measure levels of specific receptors or mRNAs in vivo. In contrast to indirect approaches, noninvasive administration of SPECT or PET gene product probes allows us to image transformed cells overexpressing each specific oncogene. We have observed that radionuclide–chelator–VIP and radionuclide–chelator–AEEA–PNA–AEEA–IGF1 analogs are effective for imaging VPAC1 receptors and CCND1 and MYCC mRNAs in breast cancer xenografts, with peptide mismatch and PNA mismatch specificity. Gene product imaging provides a route to the determination of malignancy in a suspicious mass, and molecular classification of a malignant mass.

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References

  1. American_Cancer_Society. Cancer Facts and Figures. 2008; http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf.

  2. Berg WA, Gutierrez L, NessAiver MS, et al. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology. Dec 2004;233(3):830–849.

    Article  PubMed  Google Scholar 

  3. Elmore JG, Armstrong K, Lehman CD, Fletcher SW. Screening for breast cancer. J Am Med Assoc. Mar 9, 2005;293(10):1245–1256.

    Article  CAS  Google Scholar 

  4. Rosenberg RD, Hunt WC, Williamson MR, et al. Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico. Radiology. Nov 1998;209(2):511–518.

    CAS  PubMed  Google Scholar 

  5. Brenner RJ. Breast biopsy: past, present, and future perspectives. Imaging Economics March 2006(3).

    Google Scholar 

  6. Vargas HI, Vargas MP, Gonzalez K, Burla M, Khalkhali I. Percutaneous excisional biopsy of palpable breast masses under ultrasound visualization. Breast J. Sep–Oct 2006;12(5 Suppl 2):S218–S222.

    Article  PubMed  Google Scholar 

  7. Yang WT, Tse GM. Sonographic, mammographic, and histopathologic correlation of symptomatic ductal carcinoma in situ. AJR Am J Roentgenol. Jan 2004;182(1):101–110.

    PubMed  Google Scholar 

  8. Uematsu T, Sano M, Homma K. False-positive helical CT findings of multifocal and multicentric breast cancer: is attenuation of tumor useful for diagnosing enhanced lesions? Breast Cancer. 2002;9(1):62–68.

    Article  PubMed  Google Scholar 

  9. Schnall M, Orel S. Breast MR imaging in the diagnostic setting. Magn Reson Imaging Clin N Am. Aug 2006;14(3):329-337, vi.

    Article  PubMed  Google Scholar 

  10. Ghai S, Muradali D, Bukhanov K, Kulkarni S. Nonenhancing breast malignancies on MRI: sonographic and pathologic correlation. AJR Am J Roentgenol. Aug 2005;185(2):481–487.

    PubMed  Google Scholar 

  11. Smith AP, Hall PA, Marcello DM. Emerging technologies in breast cancer detection. Radiol Manage. Jul–Aug 2004;26(4):16–24, quiz 25–17.

    PubMed  Google Scholar 

  12. Chagpar AB, Middleton LP, Sahin AA, et al. Accuracy of physical examination, ultrasonography, and mammography in predicting residual pathologic tumor size in patients treated with neoadjuvant chemotherapy. Ann Surg. Feb 2006;243(2):257–264.

    Article  PubMed  Google Scholar 

  13. Bradley JD, Perez CA, Dehdashti F, Siegel BA. Implementing biologic target volumes in radiation treatment planning for non-small cell lung cancer. J Nucl Med. Jan 2004;45(Suppl 1):96S–101S.

    PubMed  Google Scholar 

  14. Avril N, Rose CA, Schelling M, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol. Oct 15, 2000;18(20):3495–3502.

    CAS  PubMed  Google Scholar 

  15. Walter C, Scheidhauer K, Scharl A, et al. Clinical and diagnostic value of preoperative MR mammography and FDG-PET in suspicious breast lesions. Eur Radiol. Jul 2003;13(7):1651–1656.

    Article  CAS  PubMed  Google Scholar 

  16. Lenkinski RE, Ahmed M, Zaheer A, Frangioni JV, Goldberg SN. Near-infrared fluorescence imaging of microcalcification in an animal model of breast cancer. Acad Radiol. Oct 2003;10(10):1159–1164.

    Article  PubMed  Google Scholar 

  17. Song H, Shahverdi K, Huso DL, et al. An immunotolerant HER-2/neu transgenic mouse model of metastatic breast cancer. Clin Cancer Res. Oct 1, 2008;14(19):6116–6124.

    Article  CAS  PubMed  Google Scholar 

  18. Tian X, Chakrabarti A, Amirkhanov NV, et al. External imaging of CCND1, MYC, and KRAS oncogene mRNAs with tumor-targeted Radionuclide-PNA-Peptide chimeras. Ann N Y Acad Sci. Dec 2005;1059:106–144.

    Article  CAS  PubMed  Google Scholar 

  19. Chakrabarti A, Zhang K, Aruva MR, et al. Radiohybridization PET imaging of KRAS G12D mRNA expression in human pancreas cancer xenografts with [64Cu]DO3A-peptide nucleic acid-peptide nanoparticles. Cancer Biol Ther. Jun 2007;6(6):948–956.

    Article  CAS  PubMed  Google Scholar 

  20. Dewanjee MK, Haider N, Narula J. Imaging with radiolabeled antisense oligonucleotides for the detection of intracellular messenger RNA and cardiovascular disease. J Nucl Cardiol. May–Jun 1999;6(3):345–356.

    Article  CAS  PubMed  Google Scholar 

  21. Tian X, Aruva MR, Rao PS, et al. Imaging oncogene expression. In: Cho-Chung YS, Gewirtz AM, Stein CA, eds. Therapeutic Oligonucleotides: Antisense, RNAi, Triple Helix, DNA Decoys, and DNA Chips. Vol 1002. New York: New York Academy of Sciences; 2003:1083–1099.

    Google Scholar 

  22. Pickeral OK, Li JZ, Barrow I, Boguski MS, Makalowski W, Zhang J. Classical oncogenes and tumor suppressor genes: a comparative genomics perspective. Neoplasia. May–Jun 2000;2(3):280–286.

    Article  CAS  PubMed  Google Scholar 

  23. Reubi JC, Laderach U, Waser B, Gebbers JO, Robberecht P, Laissue JA. Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin. Cancer Res. Jun 1, 2000;60(11):3105–3112.

    CAS  PubMed  Google Scholar 

  24. Virgolini I, Raderer M, Kurtaran A, et al. Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors. N Engl J Med. Oct 27, 1994;331(17):1116–1121.

    Article  CAS  PubMed  Google Scholar 

  25. Moody TW, Leyton J, Gozes I, Lang L, Eckelman WC. VIP and breast cancer. Ann N Y Acad Sci. Dec 11, 1998;865:290–296.

    Article  CAS  PubMed  Google Scholar 

  26. Thakur ML, Marcus CS, Saeed S, et al . 99mTc-labeled vasoactive intestinal peptide analog for rapid localization of tumors in humans. J Nucl Med. 2000;41(1):107–110.

    CAS  PubMed  Google Scholar 

  27. Thakur ML, Aruva MR, Gariepy J, et al. PET imaging of oncogene overexpression using 64Cu-vasoactive intestinal peptide (VIP) analog: comparison with 99mTc-VIP analog. J Nucl Med. Aug 2004;45(8):1381–1389.

    CAS  PubMed  Google Scholar 

  28. Baserga R. The insulin-like growth factor I receptor: a key to tumor growth? Cancer Res. 1995;55(2):249–252.

    CAS  PubMed  Google Scholar 

  29. Armengol G, Knuutila S, Lluis F, Capella G, Miro R, Caballin MR. DNA copy number changes and evaluation of MYC, IGF1R, and FES amplification in xenografts of pancreatic adenocarcinoma. Cancer Genet Cytogenet. 2000;116(2):133–141.

    Article  CAS  PubMed  Google Scholar 

  30. Shao N, Lu S, Wickstrom E, Panchapakesan B. Integrated molecular targeting of IGF1R and Her2 surface receptors and destruction of breast cancer cells using single wall carbon nanotubes. Nanotechnology. 2007;18:315101 (315109 pp).

    Article  CAS  Google Scholar 

  31. Wang Y, Sun Y. Insulin-like growth factor receptor-1 as an anti-cancer target: blocking transformation and inducing apoptosis. Curr Cancer Drug Targets. Sep 2002;2(3):191–207.

    Article  CAS  PubMed  Google Scholar 

  32. Basu S, Wickstrom E. Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake. Bioconjug Chem. 1997;8(4):481–488.

    Article  CAS  PubMed  Google Scholar 

  33. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther. May–Jun 1999;82(2–3):241–250.

    Article  CAS  PubMed  Google Scholar 

  34. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. Jul 1995;19(3):183–232.

    Article  CAS  PubMed  Google Scholar 

  35. Goldman R, Levy RB, Peles E, Yarden Y. Heterodimerization of the erbB-1 and erbB-2 receptors in human breast carcinoma cells: a mechanism for receptor transregulation. Biochemistry. 1990;29(50):11024–11028.

    Article  CAS  PubMed  Google Scholar 

  36. Schechter AL, Hung MC, Vaidyanathan L, et al. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985;229(4717):976–978.

    Article  CAS  PubMed  Google Scholar 

  37. Kraus MH, Issing W, Miki T, Popescu NC, Aaronson SA. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci U S A. 1989;86(23):9193–9197.

    Article  CAS  PubMed  Google Scholar 

  38. Alimandi M, Romano A, Curia MC, et al. Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene. 1995;10(9):1813–1821.

    CAS  PubMed  Google Scholar 

  39. van de Vijver MJ, Peterse JL, Mooi WJ, et al. Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med. 1988;319(19):1239–1245.

    Article  PubMed  Google Scholar 

  40. Weinstat-Saslow D, Merino MJ, Manrow RE, et al. Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions. Nat Med. Dec 1995;1(12):1257–1260.

    Article  CAS  PubMed  Google Scholar 

  41. Bartkova J, Lukas J, Muller H, Strauss M, Gusterson B, Bartek J. Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer. Cancer Res. 1995;55(4):949–956.

    CAS  PubMed  Google Scholar 

  42. Adelaide J, Monges G, Derderian C, Seitz JF, Birnbaum D. Oesophageal cancer and amplification of the human cyclin D gene CCND1/PRAD1. Br J Cancer. 1995;71(1):64–68.

    Article  CAS  PubMed  Google Scholar 

  43. Gansauge S, Gansauge F, Ramadani M, et al. Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis. Cancer Res. 1997;57(9):1634–1637.

    CAS  PubMed  Google Scholar 

  44. Berns EM, Klijn JG, van Putten WL, van Staveren IL, Portengen H, Foekens JA. c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res. 1992;52(5):1107–1113.

    CAS  PubMed  Google Scholar 

  45. Wickstrom EL, Bacon TA, Gonzalez A, Freeman DL, Lyman GH, Wickstrom E. Human promyelocytic leukemia HL-60 cell proliferation and c-Myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-MYC mRNA. Proc Natl Acad Sci U S A. 1988;85(4):1028–1032.

    Article  CAS  PubMed  Google Scholar 

  46. Callagy GM, Pharoah PD, Pinder SE, et al . Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res. April 15, 2006;12(8):2468–2475.

    Article  CAS  PubMed  Google Scholar 

  47. Andrews DW, Resnicoff M, Flanders AE, et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol. 2001;19(8):2189–2200.

    CAS  PubMed  Google Scholar 

  48. Tian X, Aruva MR, Qin W, et al. External imaging of CCND1 cancer gene activity in experimental human breast cancer xenografts with 99mTc-peptide-peptide nucleic acid-peptide chimeras. J Nucl Med. Dec 2004;45(12):2070–2082.

    CAS  PubMed  Google Scholar 

  49. Kang CS, Zhang ZY, Jia ZF, et al. Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo. Cancer Gene Ther. 2006;13(5):530–538.

    Article  CAS  PubMed  Google Scholar 

  50. Vaughn JP, Iglehart JD, Demirdji S, et al. Antisense DNA downregulation of the ERBB2 oncogene measured by a flow cytometric assay. Proc Natl Acad Sci U S A. 1995;92(18):8338–8342.

    Article  CAS  PubMed  Google Scholar 

  51. Smith JB, Wickstrom E. Antisense c-myc and immunostimulatory oligonucleotide inhibition of tumorigenesis in a murine B-cell lymphoma transplant model. J Natl Cancer Inst. 1998;90(15):1146–1154.

    Article  CAS  PubMed  Google Scholar 

  52. Webb A, Cunningham D, Cotter F, et al. BCL-2 antisense therapy in patients with non-Hodgkin lymphoma. Lancet. 1997;349(9059):1137–1141.

    Article  CAS  PubMed  Google Scholar 

  53. Pallela VR, Thakur ML, Chakder S, Rattan S. 99mTc-labeled vasoactive intestinal peptide receptor agonist: functional studies. J Nucl Med. 1999;40(2):352–360.

    CAS  PubMed  Google Scholar 

  54. Tian X, Aruva MR, Zhang K, Cardi CA, Thakur ML, Wickstrom E. PET imaging of CCND1 mRNA in human MCF7 estrogen receptor-positive breast cancer xenografts with an oncogene-specific [64Cu]DO3A-PNA-peptide radiohybridization probe. J Nucl Med. Oct 2007;48(10):1699–1707.

    Article  CAS  PubMed  Google Scholar 

  55. Wickstrom E. Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors. New York: Marcel Dekker; 1998.

    Google Scholar 

  56. Good L, Nielsen PE. Progress in developing PNA as a gene-targeted drug. Antisense Nucleic Acid Drug Dev. 1997;7(4):431–437.

    CAS  PubMed  Google Scholar 

  57. Egholm M, Buchardt O, Christensen L, et al. PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature. 1993;365(6446):566–568.

    Article  CAS  PubMed  Google Scholar 

  58. Helene C, Toulme JJ. Specific regulation of gene expression by antisense, sense and antigene nucleic acids. Biochim Biophys Acta. 1990;1049(2):99–125.

    CAS  PubMed  Google Scholar 

  59. Knudsen H, Nielsen PE. Application of peptide nucleic acid in cancer therapy. Anticancer Drugs. 1997;8(2):113–118.

    Article  CAS  PubMed  Google Scholar 

  60. Gray GD, Basu S, Wickstrom E. Transformed and immortalized cellular uptake of oligodeoxynucleoside phosphorothioates, 3'-alkylamino oligodeoxynucleotides, 2'-O-methyl oligoribonucleotides, oligodeoxynucleoside methylphosphonates, and peptide nucleic acids. Biochem Pharmacol. 1997;53(10):1465–1476.

    Article  CAS  PubMed  Google Scholar 

  61. Ellis MJ, Jenkins S, Hanfelt J, et al. Insulin-like growth factors in human breast cancer. Breast Cancer Res Treat. 1998;52(1–3):175–184.

    Article  CAS  PubMed  Google Scholar 

  62. Gray GD, Wickstrom E. Rapid measurement of modified oligonucleotide levels in plasma samples with a fluorophore specific for single-stranded DNA. Antisense Nucleic Acid Drug Dev. 1997;7(3):133–140.

    CAS  PubMed  Google Scholar 

  63. Boffa LC, Cutrona G, Cilli M, et al. Therapeutically promising PNA complementary to a regulatory sequence for c-myc: pharmacokinetics in an animal model of human Burkitt’s lymphoma. Oligonucleotides. Summer 2005;15(2):85–93.

    Article  CAS  PubMed  Google Scholar 

  64. Cutrona G, Boffa LC, Mariani MR, et al. The peptide nucleic acid targeted to a regulatory sequence of the translocated c-myc oncogene in Burkitt’s lymphoma lacks immunogenicity: follow-up characterization of PNAEmu-NLS. Oligonucleotides. Spring 2007;17(1):146–150.

    Article  CAS  PubMed  Google Scholar 

  65. Boffa LC, Cutrona G, Cilli M, et al. Inhibition of Burkitt’s lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc. Cancer Gene Ther. Feb 2007;14(2):220–226.

    Article  CAS  PubMed  Google Scholar 

  66. Tian X, Aruva MR, Qin W, et al. Noninvasive molecular imaging of MYC mRNA expression in human breast cancer xenografts with a [99mTc]peptide-peptide nucleic acid-peptide chimera. Bioconjug Chem. 2005;16(1):70–79.

    Article  CAS  PubMed  Google Scholar 

  67. Sauter ER, Herlyn M, Liu SC, Litwin S, Ridge JA. Prolonged response to antisense cyclin D1 in a human squamous cancer xenograft model. Clin Cancer Res. 2000;6(2):654–660.

    CAS  PubMed  Google Scholar 

  68. Okado-Matsumoto A, Fridovich I. Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu,Zn-SOD in mitochondria. J Biol Chem. Oct 19, 2001;276(42):38388–38393.

    Article  CAS  PubMed  Google Scholar 

  69. Smith SV. Molecular imaging with copper-64. J Inorg Biochem. Nov 2004;98(11):1874–1901.

    Article  CAS  PubMed  Google Scholar 

  70. Boswell CA, Sun X, Niu W, et al. Comparative in vivo stability of copper-64-labeled cross-bridged and conventional tetraazamacrocyclic complexes. J Med Chem. Mar 11, 2004;47(6):1465–1474.

    Article  CAS  PubMed  Google Scholar 

  71. Pietrzkowski Z, Wernicke D, Porcu P, Jameson B, Baserga R. Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor 1. Cancer Res. Dec 1, 1992;52(23):6447–6451.

    CAS  PubMed  Google Scholar 

  72. Bartucci M, Morelli C, Mauro L, Ando S, Surmacz E. Differential insulin-like growth factor I receptor signaling and function in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. Cancer Res. 2001;61(18):6747–6754.

    CAS  PubMed  Google Scholar 

  73. Rao PS, Tian X, Qin W, et al. 99mTc-peptide-peptide nucleic acid probes for imaging oncogene mRNAs in tumours. Nucl Med Commun. Aug 2003;24(8):857–863.

    Article  CAS  PubMed  Google Scholar 

  74. Zhang K, Aruva MR, Shanthly N, et al. PET imaging of VPAC1 expression in experimental and spontaneous prostate cancer. J Nucl Med. Jan 2008;49(1):112–121.

    Article  CAS  PubMed  Google Scholar 

  75. Zhang K, Aruva MR, Shanthly N, et al. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) receptor specific peptide analogues for PET imaging of breast cancer: In vitro/in vivo evaluation. Regul Pept. July 6, 2007;144(1–3):91–100.

    Article  CAS  PubMed  Google Scholar 

  76. Bolin DR, Cottrell J, Garippa R, et al. Comparison of cyclic and linear analogs of vasoactive intestinal peptide. Drug Des Discov. Apr 1996;13(3–4):107–114.

    CAS  PubMed  Google Scholar 

  77. Thakur ML, Pallela VR, Consigny PM, Rao PS, Vessileva-Belnikolovska D, Shi R. Imaging vascular thrombosis with 99mTc-labeled fibrin alpha-chain peptide. J Nucl Med. 2000;41(1):161–168.

    CAS  PubMed  Google Scholar 

  78. Reubi JC. Neuropeptide receptors in health and disease: the molecular basis for in vivo imaging [see comments]. J Nucl Med. 1995;36(10):1825–1835.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by NIH CA109231, EB001809, 1S10RR23709 and PA ME-03-184 grants to M.L.T., and by DOE ER63055 and NIH C027175 to E.W.

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Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Eric Wickstrom PhD

  2. Department of Radiology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Mathew L. Thakur

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Correspondence to Mathew L. Thakur .

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  1. School of Medicine & Health Sciences, University of North Dakota, N. Columbia Road 501, Grand Forks, 58203, U.S.A.

    Edward R. Sauter

  2. Dept. Medical Oncology, Fox Chase Cancer Center, Cottman Ave. 333, Philadelphia, 19111-2497, U.S.A.

    Mary B. Daly

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Wickstrom, E., Thakur, M.L. (2010). Genetic and Molecular Approaches to Imaging Breast Cancer. In: Sauter, E., Daly, M. (eds) Breast Cancer Risk Reduction and Early Detection. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-87583-5_9

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