Seminars in Nuclear Medicine
Volume 38, Issue 1 , Pages 9-19 , January 2008

Molecular Imaging of Reporter Gene Expression in Prostate Cancer: An Overview

  • Abhinav Singh, MB, BS, BSc, MRCS

      Affiliations

    • Department of Radiology, Addenbrooke’s Hospital, Cambridge, United Kingdom.
  • ,
  • Tarik F. Massoud, MD, PhD

      Affiliations

    • Department of Radiology, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom.
    • Corresponding Author InformationAddress reprint requests to Tarik F. Massoud, MD, PhD, Department of Radiology, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Box 219, Level 5, Hills Road, Cambridge CB2 2QQ, UK.
  • ,
  • Christophe Deroose, MD, PhD

      Affiliations

    • Department of Nuclear Medicine, University Hospital Leuven, Leuven, Belgium.
  • ,
  • Sanjiv S. Gambhir, MD, PhD

      Affiliations

    • Molecular Imaging Program at Stanford (MIPS), and Departments of Radiology and Bioengineering, Bio-X Program, Stanford University School of Medicine, Stanford, CA.

References 

  1. Chokkalingam AP, Stanczyk FZ, Reichardt JK, et al. Molecular epidemiology of prostate cancer: Hormone-related genetic loci. Front Biosci. 2007;12:3436–3460
  2. Nelen V. Epidemiology of prostate cancer. Recent Results Cancer Res. 2007;175:1–8
  3. Delongchamps NB, Singh A, Haas GP. The role of prevalence in the diagnosis of prostate cancer. Cancer Control. 2006;13:158–168
  4. Tsakiris P, de la Rosette J. Imaging in genitourinary cancer from the urologists’ perspective. Cancer Imaging. 2007;7:84–92
  5. Norberg M, Egevad L, Holmberg L, et al. The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer. Urology. 1997;50:562–566
  6. Hricak H, Choyke PL, Eberhardt SC, et al. Imaging prostate cancer: A multidisciplinary perspective. Radiology. 2007;243:28–53
  7. Yu KK, Hricak H. Imaging prostate cancer. Radiol Clin North Am. 2000;38:59–85
  8. Massoud TF, Gambhir SS. Integrating noninvasive molecular imaging into molecular medicine: An evolving paradigm. Trends Mol Med. 2007;13:183–191
  9. Jaffer FA, Weissleder R. Molecular imaging in the clinical arena. JAMA. 2005;16:855–862
  10. Gross S, Piwnica-Worms D: Molecular imaging strategies for drug discovery and development. Curr Opin Chem Biol 10:334-342
  11. Hofer C, Laubenbacher C, Block T, et al. Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. Eur Urol. 1999;36:31–35
  12. Effert PJ, Bares R, Handt S, et al. Metabolic imaging of untreated prostate cancer by positron emission tomography with 18fluorine-labeled deoxyglucose. J Urol. 1996;155:994–998
  13. Fanti S, Nanni C, Ambrosini V, et al. PET in genitourinary tract cancers. Q J Nucl Med Mol Imaging. 2007;51:260–271
  14. Lawrentschuk N, Davis ID, Bolton DM, et al. Positron emission tomography and molecular imaging of the prostate: An update. BJU Int. 2006;97:923–931
  15. Karam JA, Mason RP, Koeneman KS, et al. Molecular imaging in prostate cancer. J Cell Biochem. 2003;90:473–483
  16. Powles T, Murray I, Brock C, et al. Molecular positron emission tomography and PET/CT imaging in urological malignancies. Eur Urol. 2007;51:1511–1520discussion 1520-1511
  17. Procissi D, Claus F, Burgman P, et al. In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors. Clin Cancer Res. 2007;13:3738–3747
  18. Katz S, Rosen M. MR imaging and MR spectroscopy in prostate cancer management. Radiol Clin North Am. 2006;44:723–734viii
  19. Vilanova JC, Barcelo J. Prostate cancer detection: magnetic resonance (MR) spectroscopic imaging. Abdom Imaging. 2007;32:253–261
  20. Goeb K, Engehausen DG, Krause FS, et al. MRI spectroscopy in screening of prostate cancer. Anticancer Res. 2007;27:687–693
  21. Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 2003;17:545–580
  22. Phelps ME. Inaugural article: positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci USA. 2000;97:9226–9233
  23. Gambhir SS, Barrio JR, Herschman HR, et al. Assays for noninvasive imaging of reporter gene expression. Nucl Med Biol. 1999;26:481–490
  24. Alam J, Cook JL. Reporter genes: Application to the study of mammalian gene transcription. Anal Biochem. 1990;188:245–254
  25. Serganova I, Blasberg R. Reporter gene imaging: potential impact on therapy. Nucl Med Biol. 2005;32:763–780
  26. Massoud TF: In vivo molecular imaging in oncology: Principles of reporter gene expression imaging, in Hayat MA (ed): Cancer Imaging, Vol. 2: Instrumentation and Applications. Philadelphia, Elsevier (in press)
  27. Doubrovin M, Ponomarev V, Beresten T, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci USA. 2001;98:9300–9305
  28. Green LA, Yap CS, Nguyen K, et al. Indirect monitoring of endogenous gene expression by positron emission tomography (PET) imaging of reporter gene expression in transgenic mice. Mol Imaging Biol. 2002;4:71–81
  29. Contag CH, Bachmann MH. Advances in in vivo bioluminescence imaging of gene expression. Annu Rev Biomed Eng. 2002;4:235–260
  30. Brenner M. Gene marking. Hum Gene Ther. 1996;7:1927–1936
  31. Qian DZ, Ren M, Wei Y, et al. In vivo imaging of retinoic acid receptor beta2 transcriptional activation by the histone deacetylase inhibitor MS-275 in retinoid-resistant prostate cancer cells. Prostate. 2005;64:20–28
  32. Jenkins DE, Yu SF, Hornig YS, et al. In vivo monitoring of tumor relapse and metastasis using bioluminescent PC-3M-luc-C6 cells in murine models of human prostate cancer. Clin Exp Metastasis. 2003;20:745–756
  33. Iyer M, Salazar FB, Lewis X, et al. Noninvasive imaging of enhanced prostate- specific gene expression using a two-step transcriptional amplification-based lentivirus vector. Mol Ther. 2004;10:545–552
  34. Ilagan R, Zhang LJ, Pottratz J, et al. Imaging androgen receptor function during flutamide treatment in the LAPC9 xenograft model. Mol Cancer Ther. 2005;4:1662–1669
  35. Zhang L, Johnson M, Le KH, et al. Interrogating androgen receptor function in recurrent prostate cancer. Cancer Res. 2003;63:4552–4560
  36. Seethammagari MR, Xie X, Greenberg NM, et al. EZC-prostate models offer high sensitivity and specificity for noninvasive imaging of prostate cancer progression and androgen receptor action. Cancer Res. 2006;66:6199–6209
  37. El Hilali N, Rubio N, Martinez-Villacampa M, et al. Combined noninvasive imaging and luminometric quantification of luciferase-labeled human prostate tumors and metastases. Lab Invest. 2002;82:1563–1571
  38. Yang H, Berger F, Tran C, et al. MicroPET imaging of prostate cancer in LNCAP-SR39TK-GFP mouse xenografts. Prostate. 2003;55:39–47
  39. Chemaly ER, Yoneyama R, Frangioni JV, et al. Tracking stem cells in the cardiovascular system. Trends Cardiovasc Med. 2005;15:297–302
  40. Kalikin LM, Schneider A, Thakur MA, et al. In vivo visualization of metastatic prostate cancer and quantitation of disease progression in immunocompromised mice. Cancer Biol Ther. 2003;2:656–660
  41. LeRoy BE, Thudi NK, Nadella MV, et al. New bone formation and osteolysis by a metastatic, highly invasive canine prostate carcinoma xenograft. Prostate. 2006;66:1213–1222
  42. Brakenhielm E, Burton JB, Johnson M, et al. Modulating metastasis by a lymphangiogenic switch in prostate cancer. Int J Cancer. 2007;121:2153–2161
  43. Min JJ, Gambhir SS. Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects. Gene Ther. 2004;11:115–125
  44. Figueiredo ML, Kao C, Wu L. Advances in preclinical investigation of prostate cancer gene therapy. Mol Ther. 2007;15:1053–1064
  45. Dobosy JR, Roberts JL, Fu VX, et al. The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia. J Urol. 2007;177:822–831
  46. Li LC. Epigenetics of prostate cancer. Front Biosci. 2007;12:3377–3397
  47. Ray P, Bauer E, Iyer M, et al. Monitoring gene therapy with reporter gene imaging. Semin Nucl Med. 2001;31:312–320
  48. Sato M, Johnson M, Zhang L, et al. Optimization of adenoviral vectors to direct highly amplified prostate-specific expression for imaging and gene therapy. Mol Ther. 2003;8:726–737
  49. Iyer M, Salazar FB, Wu L, et al. Bioluminescence imaging of systemic tumor targeting using a prostate-specific lentiviral vector. Hum Gene Ther. 2006;17:125–132
  50. Li H, Li JZ, Helm GA, et al. Non-invasive imaging of firefly luciferase reporter gene expression using bioluminescence imaging in human prostate cancer models. Biotechnol Appl Biochem. 2007;46:179–184
  51. Sato M, Johnson M, Zhang L, et al. Functionality of androgen receptor-based gene expression imaging in hormone refractory prostate cancer. Clin Cancer Res. 2005;11:3743–3749
  52. Johnson M, Sato M, Burton J, et al. Micro-PET/CT monitoring of herpes thymidine kinase suicide gene therapy in a prostate cancer xenograft: The advantage of a cell-specific transcriptional targeting approach. Mol Imaging. 2005;4:463–472
  53. Pantuck AJ, Berger F, Zisman A, et al. CL1-SR39: A noninvasive molecular imaging model of prostate cancer suicide gene therapy using positron emission tomography. J Urol. 2002;168:1193–1198
  54. Siddiqui F, Barton KN, Stricker HJ, et al. Design considerations for incorporating sodium iodide symporter reporter gene imaging into prostate cancer gene therapy trials. Hum Gene Ther. 2007;18:312–322
  55. Liu L, Kodibagkar VD, Yu JX, et al. 19F-NMR detection of lacZ gene expression via the enzymic hydrolysis of 2-fluoro-4-nitrophenyl beta-D-galactopyranoside in vivo in PC3 prostate tumor xenografts in the mouse. Faseb J. 2007;21:2014–2019
  56. Greenberg NM, DeMayo F, Finegold MJ, et al. Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA. 1995;92:3439–3443
  57. Kim MJ, Bhatia-Gaur R, Banach-Petrosky WA, et al. Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis. Cancer Res. 2002;62:2999–3004
  58. Masumori N, Thomas TZ, Chaurand P, et al. A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential. Cancer Res. 2001;61:2239–2249
  59. Gao H, Ouyang X, Banach-Petrosky W, et al. A critical role for p27kip1 gene dosage in a mouse model of prostate carcinogenesis. Proc Natl Acad Sci USA. 2004;101:17204–17209
  60. Wang S, Gao J, Lei Q, et al. Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell. 2003;4:209–221
  61. Ellwood-Yen K, Graeber TG, Wongvipat J, et al. Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell. 2003;4:223–238
  62. Singh AS, Figg WD. In vivo models of prostate cancer metastasis to bone. J Urol. 2005;174:820–826
  63. Xie X, Luo Z, Slawin KM, et al. The EZC-prostate model: noninvasive prostate imaging in living mice. Mol Endocrinol. 2004;18:722–732
  64. Lyons SK, Lim E, Clermont AO, et al. Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice. Cancer Res. 2006;66:4701–4707
  65. Hsieh CL, Xie Z, Liu ZY, et al. A luciferase transgenic mouse model: visualization of prostate development and its androgen responsiveness in live animals. J Mol Endocrinol. 2005;35:293–304
  66. Hsieh CL, Xie Z, Yu J, et al. Non-invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model. Prostate. 2007;67:685–691
  67. Massoud TF, Paulmurugan R, De A, et al. Reporter gene imaging of protein-protein interactions in living subjects. Curr Opin Biotechnol. 2007;18:31–37
  68. Ilagan R, Pottratz J, Le K, et al. Imaging mitogen-activated protein kinase function in xenograft models of prostate cancer. Cancer Res. 2006;66:10778–10785
  69. Kim SB, Ozawa T, Watanabe S, et al. High-throughput sensing and noninvasive imaging of protein nuclear transport by using reconstitution of split Renilla luciferase. Proc Natl Acad Sci USA. 2004;101:11542–11547
  70. Ray P, De A, Min JJ, et al. Imaging tri-fusion multimodality reporter gene expression in living subjects. Cancer Res. 2004;64:1323–1330
  71. Pomper MG. Translational molecular imaging for cancer. Cancer Imaging. 2005;5 Spec No A:S16–S26
  72. Somia N, Verma IM. Gene therapy: trials and tribulations. Nat Rev Genet. 2000;1:91–99
  73. Yaghoubi S, Barrio JR, Dahlbom M, et al. Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. J Nucl Med. 2001;42:1225–1234
  74. Yaghoubi SS, Couto MA, Chen CC, et al. Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk’s expression. J Nucl Med. 2006;47:706–715
  75. Jacobs A, Voges J, Reszka R, et al. Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet. 2001;358:727–729
  76. Penuelas I, Mazzolini G, Boan JF, et al. Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology. 2005;128:1787–1795
  77. Lee KC, Sud S, Meyer CR, et al. An imaging biomarker of early treatment response in prostate cancer that has metastasized to the bone. Cancer Res. 2007;67:3524–3528

PII: S0001-2998(07)00093-1

doi: 10.1053/j.semnuclmed.2007.09.002

Seminars in Nuclear Medicine
Volume 38, Issue 1 , Pages 9-19 , January 2008