Skip to main content

Functional Molecular Imaging of Prostate Cancer Lymph Node Metastases: Adenovirus-Mediated Lymph Node Detection

  • Chapter
  • First Online:
Book cover From Local Invasion to Metastatic Cancer

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

  • 916 Accesses

Abstract

Like other solid epithelial tumors, nodal involvement in prostate cancer signifies a poor clinical outcome. Yet, the lack of standard pelvic lymph node (LN)-sampling procedures and specific noninvasive imaging approaches to accurately assess nodal involvement is hampering the management decision. This chapter will discuss the debates in the clinical community on LN dissection and the development of various imaging modalities for prostate cancer. We will also describe a novel approach of using recombinant human adenoviral vectors (Ads) to directly map nodal metastases in experimental models of human prostate cancer. By exploiting the innate lymphotrophic properties of adenovirus and the prostate-restricted expression of imaging reporter genes incorporated into the viral vector, we were able to produce bioluminescent or positron emission tomography (PET) signals that correlate with the presence of metastatic lesions in the draining LNs. Significantly, this approach enables the direct PET visualization of sentinel lymph node (SLN) metastases, without the need for lymphadenectomy. We believe that developing and implementing more effective diagnostic imaging modalities to assess nodal status could improve the outcomes for patients with advanced stage prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol 2004;172(3):910–4.

    Article  PubMed  Google Scholar 

  2. Epstein JI, Partin AW, Potter SR, Walsh PC. Adenocarcinoma of the prostate invading the seminal vesicle: prognostic stratification based on pathologic parameters. Urology 2000;56(2):283–8.

    Article  PubMed  CAS  Google Scholar 

  3. Daneshmand S, Quek ML, Stein JP, et al. Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results. J Urol 2004;172(6 Pt 1):2252–5.

    Article  PubMed  Google Scholar 

  4. Cheng L, Zincke H, Blute ML, Bergstralh EJ, Scherer B, Bostwick DG. Risk of prostate carcinoma death in patients with lymph node metastasis. Cancer 2001;91(1):66–73.

    Article  PubMed  CAS  Google Scholar 

  5. Link RE, Morton RA. Indications for pelvic lymphadenectomy in prostate cancer. Urol Clin North Am 2001;28(3):491–8.

    Article  PubMed  CAS  Google Scholar 

  6. Turkeri L. The extent of lymph node dissection in patients with localised prostate cancer: debate continues. Eur Urol 2007;51(6):1472–4.

    Article  PubMed  Google Scholar 

  7. Klein EA, Kattan M, Stephenson A, Vickers A. How many lymphadenectomies does it take to cure one patient? Eur Urol 2008;53(1):13–5; discussion 8–20.

    Article  PubMed  Google Scholar 

  8. Bader P, Burkhard FC, Markwalder R, Studer UE. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol 2003;169(3):849–54.

    Article  PubMed  Google Scholar 

  9. Allaf ME, Palapattu GS, Trock BJ, Carter HB, Walsh PC. Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J Urol 2004;172(5 Pt 1):1840–4.

    Article  PubMed  Google Scholar 

  10. Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 2006;68(1):121–5.

    Article  PubMed  Google Scholar 

  11. Berglund RK, Sadetsky N, DuChane J, Carroll PR, Klein EA. Limited pelvic lymph node dissection at the time of radical prostatectomy does not affect 5-year failure rates for low, intermediate and high risk prostate cancer: results from CaPSURE. J Urol 2007;177(2):526–9; discussion 9–30.

    Article  PubMed  Google Scholar 

  12. DiMarco DS, Zincke H, Sebo TJ, Slezak J, Bergstralh EJ, Blute ML. The extent of lymphadenectomy for pTXNO prostate cancer does not affect prostate cancer outcome in the prostate specific antigen era. J Urol 2005;173(4):1121–5.

    Article  PubMed  Google Scholar 

  13. Beck SD, Foster RS. Long-term outcome of retroperitoneal lymph node dissection in the management of testis cancer. World J Urol 2006;24(3):267–72.

    Article  PubMed  Google Scholar 

  14. Konety BR, Joslyn SA, O’Donnell MA. Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the Surveillance, Epidemiology and End Results Program data base. J Urol 2003;169(3):946–50.

    Article  PubMed  Google Scholar 

  15. Steven K, Poulsen AL. Radical cystectomy and extended pelvic lymphadenectomy: survival of patients with lymph node metastasis above the bifurcation of the common iliac vessels treated with surgery only. J Urol 2007;178(4 Pt 1):1218–23; discussion 23–4.

    Article  PubMed  Google Scholar 

  16. Cabanas RM. An approach for the treatment of penile carcinoma. Cancer 1977;39(2):456–66.

    Article  PubMed  CAS  Google Scholar 

  17. Hungerhuber E, Schlenker B, Karl A, et al. Risk stratification in penile carcinoma: 25-year experience with surgical inguinal lymph node staging. Urology 2006;68(3):621–5.

    Article  PubMed  Google Scholar 

  18. Lynch Jr DaS, PF. Tumors of the penis. In: PC Walsh, AB Retik and ED Vaughan Jr, et al. Campbells’ Urology 1998;3:2453–85.

    Google Scholar 

  19. Fraley EE, Zhang G, Manivel C, Niehans GA. The role of ilioinguinal lymphadenectomy and significance of histological differentiation in treatment of carcinoma of the penis. J Urol 1989;142(6):1478–82.

    PubMed  CAS  Google Scholar 

  20. Spiess PE, Izawa JI, Bassett R, et al. Preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging penile cancer: results with pathological correlation. J Urol 2007;177(6):2157–61.

    Article  PubMed  Google Scholar 

  21. Han M, Partin AW, Pound CR, Epstein JI, Walsh PC. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am 2001;28(3):555–65.

    Article  PubMed  CAS  Google Scholar 

  22. Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur Urol 2007;52(1):29–37.

    Article  PubMed  Google Scholar 

  23. Mattei A, Fuechsel FG, Bhatta Dhar N, et al. The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study. Eur Urol 2008;53(1):118–25.

    Article  PubMed  Google Scholar 

  24. Touijer K, Rabbani F, Otero JR, et al. Standard versus limited pelvic lymph node dissection for prostate cancer in patients with a predicted probability of nodal metastasis greater than 1%. J Urol 2007;178(1):120–4.

    Article  PubMed  Google Scholar 

  25. Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003;348(25):2491–9.

    Article  PubMed  Google Scholar 

  26. Harisinghani MG, Weissleder R. Sensitive, noninvasive detection of lymph node metastases. PLoS Med 2004;1(3):e66.

    Article  PubMed  Google Scholar 

  27. Effert PJ, Bares R, Handt S, Wolff JM, Bull U, Jakse G. Metabolic imaging of untreated prostate cancer by positron emission tomography with 18fluorine-labeled deoxyglucose. J Urol 1996;155(3):994–8.

    Article  PubMed  CAS  Google Scholar 

  28. Oyama N, Akino H, Kanamaru H, et al. 11C-acetate PET imaging of prostate cancer. J Nucl Med 2002;43(2):181–6.

    PubMed  CAS  Google Scholar 

  29. de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-choline PET. J Nucl Med 2003;44(3):331–5.

    PubMed  Google Scholar 

  30. Hadway P, Lynch M, Heenan S, Watkin NA. Current status of dynamic lymphoscintigraphy and sentinel lymph-node biopsy in urological malignancies. BJU Int 2005;96(9):1235–9.

    Article  PubMed  Google Scholar 

  31. Kishimoto H, Kojima T, Watanabe Y, et al. In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus. Nat Med 2006;12(10):1213–9.

    Article  PubMed  CAS  Google Scholar 

  32. Burton JB, Johnson M, Sato M, Koh SB, Mulholland DJ, Stout D, Chatziioannou AF, Phelps ME, Wu H, Wu L. Adenovirus mediated gene expression imaging to directly detect sentinel lymph node metastasis of prostate cancer. Nat Med 2008;14(8):882–8.

    Google Scholar 

  33. Barrett T, Choyke PL, Kobayashi H. Imaging of the lymphatic system: new horizons. Contrast Media Mol Imaging 2006;1(6):230–45.

    Article  PubMed  CAS  Google Scholar 

  34. Szuba A, Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med 2003;44(1):43–57.

    PubMed  Google Scholar 

  35. Ikomi F, Hanna GK, Schmid-Schonbein GW. Size- and surface-dependent uptake of colloid particles into the lymphatic system. Lymphology 1999;32(3):90–102.

    PubMed  CAS  Google Scholar 

  36. Rowe WP, Huebner RJ, Gilmore LK, Parrott RH, Ward TG. Isolation of a cytopathogenic agent from human adenoids undergoing spontaneous degeneration in tissue culture. Proc Soc Exp Biol Med 1953;84(3):570–3.

    PubMed  CAS  Google Scholar 

  37. Johnson M, Huyn S, Burton J, Sato M, Wu L. Differential biodistribution of adenoviral vector in vivo as monitored by bioluminescence imaging and quantitative polymerase chain reaction. Hum Gene Ther 2006;17(12):1262–9.

    Article  PubMed  CAS  Google Scholar 

  38. Iyer M, Wu L, Carey M, Wang Y, Smallwood A, Gambhir SS. Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters. Proc Natl Acad Sci USA 2001;98(25):14595–600.

    Article  PubMed  CAS  Google Scholar 

  39. Emami KH, Carey M. A synergistic increase in potency of a multimerized VP16 transcriptional activation domain. EMBO J 1992;11(13):5005–12.

    PubMed  CAS  Google Scholar 

  40. Sato M, Johnson M, Zhang L, Gambhir SS, Carey M, Wu L. Functionality of androgen receptor-based gene expression imaging in hormone refractory prostate cancer. Clin Cancer Res 2005;11(10):3743–9.

    Article  PubMed  CAS  Google Scholar 

  41. Zhang L, Adams JY, Billick E, et al. Molecular engineering of a two-step transcription amplification (TSTA) system for transgene delivery in prostate cancer. Mol Ther 2002;5(3):223–32.

    Article  PubMed  CAS  Google Scholar 

  42. Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003;17(5):545–80.

    Article  PubMed  CAS  Google Scholar 

  43. Brakenhielm E, Burton JB, Johnson M, et al. Modulating metastasis by a lymphangiogenic switch in prostate cancer. Int J Cancer 2007;121(10):2153–61.

    Article  PubMed  CAS  Google Scholar 

  44. Johnson M, Sato M, Burton J, Gambhir SS, Carey M, Wu L. 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(4):463–72.

    PubMed  Google Scholar 

  45. Burton JB, Priceman SJ, Sung JL, Pytowski B, Alitalo K, Wu L. Suppression of prostate cancer nodal and systemic metastasis by blockade of the lymphangiogenic axis. Cancer Res 2008;68(19):7828–37.

    Google Scholar 

  46. Pantuck AJ, Matherly J, Zisman A, et al. Optimizing prostate cancer suicide gene therapy using herpes simplex virus thymidine kinase active site variants. Hum Gene Ther 2002;13(7):777–89.

    Article  PubMed  CAS  Google Scholar 

  47. Yaghoubi SS, Barrio JR, Namavari M, et al. Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography. Cancer Gene Ther 2005;12(3):329–39.

    Article  PubMed  CAS  Google Scholar 

  48. Huyn et al. A Potent, Imaging Adenoviral Vector Driven by the Cancer-Selective Mucin-1 Promoter that Targets Breast Cancer Metastasis, submitted.

    Google Scholar 

Download references

Acknowledgement

We thank Ms. Sok Boon Koh for performing the electron microscopy of adenovirus and providing the images. This work is supported by NCI SPORE program P50 CA092131, RO1 CA101904, and Prostate Cancer Foundation. J.B. is supported by Department of Defense, CDMRP 07-1-0064 (prostate cancer predoctoral training grant). S.P. is supported by the career developmental program of UCLA ICMIC (P50 CA86306 to H.R. Herschman) grant.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

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

About this chapter

Cite this chapter

Priceman, S.J., Burton, J.B., Wu, L. (2009). Functional Molecular Imaging of Prostate Cancer Lymph Node Metastases: Adenovirus-Mediated Lymph Node Detection. 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_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-087-8_16

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-086-1

  • Online ISBN: 978-1-60327-087-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics