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Molecular Imaging of Cancer: Receptors, Angiogenesis, and Gene Expression

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From Local Invasion to Metastatic Cancer

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

There is an increasing desire to understand molecular mechanisms that regulate cancer growth and metastasis. Positron emission tomography (PET) imaging can be used for this purpose in research and clinical trials. An ever-growing number of PET tracers are now available to image biochemical alterations characteristic of the cancer cell or tumor-induced changes in the surrounding stroma. This chapter addresses angiogenesis, receptor expression, and gene imaging. Angiogenesis can be imaged using the compound 18F arginine–glycine–aspartic acid (RGD) peptide, which binds specifically to ανβ3 integrin receptors expressed at the surface of proliferating endothelial cells. A number of receptors are critical for cancer development and progression. Presence and functional activity of receptors can be studied with PET probes, among which FDHT and FES are in clinical trials for imaging of the androgen and estrogen receptors, respectively. Gene expression can be imaged, and this will be of increasing importance as part of future clinical trials with stem cells or modified T cells, allowing for cell tracking in the human body and visualization of the degree and location of expression of a therapeutic gene.

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References

  1. Folkman J. Angiogenesis: An organizing principle for drug discovery? Nat Rev Drug Discov 2007;6:273–86.

    Article  PubMed  CAS  Google Scholar 

  2. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57–70.

    Article  PubMed  CAS  Google Scholar 

  3. Phelps M. Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci USA 2000;97:9226–33.

    Article  PubMed  CAS  Google Scholar 

  4. Warburg O. The Metabolism of Tumors. New York, NY: Richard R. Smith, 1931.

    Google Scholar 

  5. Schoder H, Glass EC, Pecking AP, et al. Molecular targeting of the lymphovascular system for imaging and therapy. Cancer Metastasis Rev 2006;25:185–201.

    Article  PubMed  Google Scholar 

  6. Folkman J. Angiogenesis. Annu Rev Med 2006;57:1–18.

    Article  PubMed  CAS  Google Scholar 

  7. Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1995;1:149–53.

    Article  PubMed  CAS  Google Scholar 

  8. Naumov GN, Akslen LA, Folkman J. Role of angiogenesis in human tumor dormancy: animal models of the angiogenic switch. Cell Cycle 2006;5:1779–87.

    Article  PubMed  CAS  Google Scholar 

  9. Almog N, Henke V, Flores L, et al. Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis. FASEB J 2006;20:947–9.

    Article  PubMed  CAS  Google Scholar 

  10. Haubner R, Weber WA, Beer AJ, et al. Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD. PLoS Med 2005;2: e70.

    Article  PubMed  Google Scholar 

  11. Beer AJ, Grosu AL, Carlsen J, et al. [18F]galacto-RGD positron emission tomography for imaging of alphavbeta3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res 2007;13:6610–6.

    Article  PubMed  CAS  Google Scholar 

  12. Beer AJ, Haubner R, Sarbia M, et al. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 2006;12:3942–9.

    Article  PubMed  CAS  Google Scholar 

  13. Beer AJ, Niemeyer M, Carlsen J, et al. Patterns of {alpha}v{beta}3 expression in primary and metastatic human breast cancer as shown by 18F-Galacto-RGD PET. J Nucl Med 2008;49:255–9.

    Article  PubMed  Google Scholar 

  14. Larson SM, Morris M, Gunther I, et al. Tumor localization of 16beta- (18)F-fluoro-5alpha-dihydrotestosterone versus (18)F-FDG in patients with progressive, metastatic prostate cancer. J Nucl Med 2004;45:366–73.

    PubMed  CAS  Google Scholar 

  15. Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 2001;19:2797–803.

    PubMed  CAS  Google Scholar 

  16. Peterson LM, Mankoff DA, Lawton T, et al. Quantitative imaging of estrogen receptor expression in breast cancer with PET and 18F-fluoroestradiol. J Nucl Med 2008;49:367–374.

    Google Scholar 

  17. Smith-Jones PM, Solit DB, Akhurst T, Afroze F, Rosen N, Larson SM. Imaging the pharmacodynamics of HER2 degradation in response to Hsp90 inhibitors. Nat Biotechnol 2004;22:701–6.

    Article  PubMed  CAS  Google Scholar 

  18. Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004;10:33–9.

    Article  PubMed  Google Scholar 

  19. Pienta KJ, Bradley D. Mechanisms underlying the development of androgen-independent prostate cancer. Clin Cancer Res 2006;12:1665–71.

    Article  PubMed  CAS  Google Scholar 

  20. Yoshida T, Kinoshita H, Segawa T, et al. Antiandrogen bicalutamide promotes tumor growth in a novel androgen-dependent prostate cancer xenograft model derived from a bicalutamide-treated patient. Cancer Res 2005;65:9611–6.

    Article  PubMed  CAS  Google Scholar 

  21. Solit DB, Zheng FF, Drobnjak M, et al. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res 2002;8:986–93.

    PubMed  CAS  Google Scholar 

  22. Liao X, Tang S, Thrasher JB, Griebling TL, Li B. Small-interfering RNA-induced androgen receptor silencing leads to apoptotic cell death in prostate cancer. Mol Cancer Ther 2005;4:505–15.

    Article  PubMed  CAS  Google Scholar 

  23. Cheng H, Snoek R, Ghaidi F, Cox ME, Rennie PS. Short hairpin RNA knockdown of the androgen receptor attenuates ligand-independent activation and delays tumor progression. Cancer Res 2006;66:10613–20.

    Article  PubMed  CAS  Google Scholar 

  24. Choe YS, Lidstrom PJ, Chi DY, Bonasera TA, Welch MJ, Katzenellenbogen JA. Synthesis of 11 beta-[18F]fluoro-5 alpha-dihydrotestosterone and 11 beta-[18F]fluoro-19-nor-5 alpha-dihydrotestosterone: preparation via halofluorination-reduction, receptor binding, and tissue distribution. J Med Chem 1995;38:816–25.

    Article  PubMed  CAS  Google Scholar 

  25. Dehdashti F, Picus J, Michalski JM, et al. Positron tomographic assessment of androgen receptors in prostatic carcinoma. Eur J Nucl Med Mol Imaging 2005;32:344–50.

    Article  PubMed  Google Scholar 

  26. Hara T, Miyazaki H, Lee A, Tran CP, Reiter RE. Androgen receptor and invasion in prostate cancer. Cancer Res 2008;68:1128–35.

    Article  PubMed  CAS  Google Scholar 

  27. Ravdin PM, Green S, Dorr TM, et al. Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study. J Clin Oncol 1992;10:1284–91.

    PubMed  CAS  Google Scholar 

  28. Cristofanilli M, Krishnamurthy S, Guerra L, et al. A nonreplicating adenoviral vector that contains the wild-type p53 transgene combined with chemotherapy for primary breast cancer: safety, efficacy, and biologic activity of a novel gene-therapy approach. Cancer 2006;107:935–44.

    Article  PubMed  CAS  Google Scholar 

  29. Sterman DH, Recio A, Vachani A, et al. Long-term follow-up of patients with malignant pleural mesothelioma receiving high-dose adenovirus herpes simplex thymidine kinase/ganciclovir suicide gene therapy. Clin Cancer Res 2005;11:7444–53.

    Article  PubMed  CAS  Google Scholar 

  30. Aiuti A, Bachoud-Levi AC, Blesch A, et al. Progress and prospects: gene therapy clinical trials (part 2). Gene Ther 2007;14:1555–63.

    Article  PubMed  Google Scholar 

  31. Tuszynski MH, Thal L, Pay M, et al. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 2005;11:551–5.

    Article  PubMed  CAS  Google Scholar 

  32. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000;288:669–72.

    Article  PubMed  CAS  Google Scholar 

  33. Min JJ, Gambhir SS. Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects. Gene Ther 2004;11:115–25.

    PubMed  CAS  Google Scholar 

  34. Tjuvajev JG, Stockhammer G, Desai R, et al. Imaging the expression of transfected genes in vivo. Cancer Res 1995;55:6126–32.

    PubMed  CAS  Google Scholar 

  35. Gambhir SS, Barrio JR, Wu L, et al. Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir. J Nucl Med 1998;39:2003–11.

    PubMed  CAS  Google Scholar 

  36. Shah K, Jacobs A, Breakefield XO, Weissleder R. Molecular imaging of gene therapy for cancer. Gene Ther 2004;11:1175–87.

    Article  PubMed  CAS  Google Scholar 

  37. Penuelas I, Mazzolini G, Boan JF, et al. Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology 2005;128:1787–95.

    Article  PubMed  CAS  Google Scholar 

  38. Mackensen A, Meidenbauer N, Vogl S, Laumer M, Berger J, Andreesen R. Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cells for the treatment of patients with metastatic melanoma. J Clin Oncol 2006;24:5060–9.

    Article  PubMed  CAS  Google Scholar 

  39. Morgan RA, Dudley ME, Wunderlich JR, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006;314:126–9.

    Article  PubMed  CAS  Google Scholar 

  40. Li Z, Wu JC, Sheikh AY, et al. Differentiation, survival, and function of embryonic stem cell derived endothelial cells for ischemic heart disease. Circulation 2007;116:I46–54.

    PubMed  Google Scholar 

  41. Hauger O, Frost EE, van Heeswijk R, et al. MR evaluation of the glomerular homing of magnetically labeled mesenchymal stem cells in a rat model of nephropathy. Radiology 2006;238:200–10.

    Article  PubMed  Google Scholar 

  42. Wu X, Hu J, Zhou L, et al. In vivo tracking of superparamagnetic iron oxide nanoparticle-labeled mesenchymal stem cell tropism to malignant gliomas using magnetic resonance imaging. Laboratory investigation. J Neurosurg 2008;108:320–9.

    Article  PubMed  Google Scholar 

  43. Jacobs AH, Rueger MA, Winkeler A, et al. Imaging-guided gene therapy of experimental gliomas. Cancer Res 2007;67:1706–15.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiology/Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Heiko Schöder MD

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  1. Heiko Schöder MD
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Editors and Affiliations

  1. Division of Surgical Oncology, University of California, San Francisco, Divisadero St. 1600, San Francisco, 94115, USA

    Stanley P. L. Leong

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Schöder, H. (2009). Molecular Imaging of Cancer: Receptors, Angiogenesis, and Gene Expression. In: Leong, S. (eds) From Local Invasion to Metastatic Cancer. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-087-8_10

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  • DOI: https://doi.org/10.1007/978-1-60327-087-8_10

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-086-1

  • Online ISBN: 978-1-60327-087-8

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