Skip to main content
SpringerLink
Log in

Role of ICG-99mTc-nanocolloid for sentinel lymph node detection in cervical cancer: a pilot study

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early cervical cancer. For this purpose, the tracers most commonly used are radiotracers based on technetium. For the last decade, indocyanine green (ICG) has been used as a tracer for SLNB in other malignancies with excellent results and, more recently, a combination of ICG and a radiotracer has been shown to have the advantages of both tracers. The aim of this study was to evaluate the role of ICG-99mTc-nanocolloid in SLN detection in patients with cervical cancer.

Methods

This prospective study included 16 patients with cervical cancer. The hybrid tracer was injected the day (19–21 h) before surgery for planar and SPECT/CT lymphoscintigraphy. Blue dye was administered periorificially in 14 patients. SLNs were removed according to their distribution on lymphoscintigraphy and when radioactive, fluorescent and/or stained with blue dye. Nodal specimens were pathologically analysed for metastases including by immunochemistry.

Results

Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69 SLNs were removed, of which 66 were detected by their radioactivity signal and 67 by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14 patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases were diagnosed in two patients, and were the only lymphatic nodes involved.

Conclusions

SLNB with ICG-99mTc-nanocolloid is feasible and safe in patients with early cervical cancer. This hybrid tracer provided bilateral SLN detection in all patients and a higher detection rate than blue dye, so it could become an alternative to the combined technique.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Stehman FB, Bundy BN, DiSaia PJ, Keys HM, Larson JE, Fowler WC. Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer. 1991;67:2776–85.

    Article  CAS  PubMed  Google Scholar 

  2. Waggoner SE. Cervical cancer. Lancet. 2003;361:2217–25.

    Article  PubMed  Google Scholar 

  3. Cibula D, Abu-Rustum NR, Dusek L, Zikán M, Zaal A, Sevcik L, et al. Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer. Gynecol Oncol. 2012;124:496–501.

    Article  CAS  PubMed  Google Scholar 

  4. Miccò M, Sala E, Lakhman Y, Hricak H, Vargas HA. Role of imaging in the pretreatment evaluation of common gynecological cancers. Womens Health (Lond). 2014;10:299–321.

    Article  Google Scholar 

  5. Giammarile F, Bozkurt M, Cibula D, Pahisa J, Oyen W, Paredes P, et al. The EANM clinical and technical guidelines for lymphoscintigraphy and sentinel node localization in gynaecological cancers. Eur J Nucl Med Mol Imaging. 2014;41:1463–77.

    Article  PubMed  Google Scholar 

  6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines©): Cervical Cancer. Fort Washington, PA: National Comprehensive Cancer Network; 2017.

  7. Rob L, Strnad P, Robova H, Charvat M, Pluta M, Schlegerova D, et al. Study of lymphatic mapping and sentinel node identification in early stage cervical cancer. Gynecol Oncol. 2005;98:281–8.

    Article  PubMed  Google Scholar 

  8. Paredes P, Vidal-Sicart S, García S, Pahisa J, Torné A, Ordi J, et al. Usefulness of the sentinel node in the treatment and staging of initial cervix cancer. Rev Esp Med Nucl. 2004;23:253–8.

    Article  CAS  PubMed  Google Scholar 

  9. Collarino A, Vidal-Sicart S, Perotti G, Valdes Olmos RA. The sentinel node approach in gynaecological malignancies. Clin Transl Imaging. 2016;4:411–20.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Domenech B, Paredes P, Rubí S, Pahisa J, Vidal-Sicart S, Pons F. Mirror-image lymph node in FDG PET/CT and SPECT/CT for sentinel node detection. Clin Nucl Med. 2014;39:e241–2.

    Article  PubMed  Google Scholar 

  11. Jeschke S, Beri A, Grüll M, Ziegerhofer J, Prammer P, Leeb K, et al. Laparoscopic radioisotope-guided sentinel lymph node dissection in staging of prostate cancer. Eur Urol. 2008;53:126–32.

    Article  PubMed  Google Scholar 

  12. Namikawa K, Yamazaki N. Sentinel lymph node biopsy guided by indocyanine green fluorescence for cutaneous melanoma. Eur J Dermatol. 2011;21:184–90.

    PubMed  Google Scholar 

  13. Kitai T, Kawashima M. Transcutaneous detection and direct approach to the sentinel node using axillary compression technique in ICG fluorescence-navigated sentinel node biopsy for breast cancer. Breast Cancer. 2012;19:343–8.

    Article  PubMed  Google Scholar 

  14. Schaafsma BE, Verbeek FP, Peters AA, van der Vorst JR, de Kroon CD, van Poelgeest MI, et al. Near-infrared fluorescence sentinel lymph node biopsy in vulvar cancer: a randomised comparison of lymphatic tracers. BJOG. 2013;120:758–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Plante M, Touhami O, Trinh X-B, Renaud M-C, Sebastianelli A, Grondin K, et al. Sentinel node mapping with indocyanine green and endoscopic near-infrared fluorescence imaging in endometrial cancer. A pilot study and review of the literature. Gynecol Oncol. 2015;137:443–7.

    Article  PubMed  Google Scholar 

  16. Stoffels I, Leyh J, Pöppel T, Schadendorf D, Klode J. Evaluation of a radioactive and fluorescent hybrid tracer for sentinel lymph node biopsy in head and neck malignancies: prospective randomized clinical trial to compare ICG-(99m)Tc-nanocolloid hybrid tracer versus (99m)Tc-nanocolloid. Eur J Nucl Med Mol Imaging. 2015;42:1631–8.

    Article  CAS  PubMed  Google Scholar 

  17. Crane LM, Themelis G, Arts HJ, Buddingh KT, Brouwers AH, Ntziachristos V, et al. Intraoperative near-infrared fluorescence imaging for sentinel lymph node detection in vulvar cancer: first clinical results. Gynecol Oncol. 2011;120:291–5.

    Article  CAS  PubMed  Google Scholar 

  18. Sinno AK, Fader AN, Roche KL, Giuntoli RL, Tanner EJ. A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer. Gynecol Oncol. 2014;134:281–6.

    Article  PubMed  Google Scholar 

  19. Diab Y. Sentinel lymph nodes mapping in cervical cancer a comprehensive review. Int J Gynecol Cancer. 2017;27:154–8.

    Article  PubMed  Google Scholar 

  20. Hutteman M, van der Vorst JR, Gaarenstroom KN, Peters AA, Mieog JS, Schaafsma BE, et al. Optimization of near-infrared fluorescent sentinel lymph node mapping for vulvar cancer. Am J Obstet Gynecol. 2013;206:89.e1–5

    Article  Google Scholar 

  21. Mathéron HM, van den Berg NS, Brouwer OR, Kleinjan GH, van Driel WJ, Trum JW, et al. Multimodal surgical guidance towards the sentinel node in vulvar cancer. Gynecol Oncol. 2013;131:720–5.

    Article  PubMed  Google Scholar 

  22. Crane LM, Themelis G, Pleijhuis RG, Harlaar NJ, Sarantopoulos A, Arts HJ, et al. Intraoperative multispectral fluorescence imaging for the detection of the sentinel lymph node in cervical cancer: a novel concept. Mol Imaging Biol. 2011;13:1043–9.

    Article  PubMed  Google Scholar 

  23. Buckle T, Chin PT, van Leeuwen FW. (Non-targeted) radioactive/fluorescent nanoparticles and their potential in combined pre- and intraoperative imaging during sentinel lymph node resection. Nanotechnology. 2010;21:482001.

    Article  PubMed  Google Scholar 

  24. van der Poel HG, Buckle T, Brouwer OR, Valdés Olmos RA, van Leeuwen FWB. Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer. Eur Urol. 2011;60:826–33.

    Article  PubMed  Google Scholar 

  25. KleinJan GH, Bunschoten A, van den Berg NS, Olmos RA, Klop WM, Horenblas S, et al. Fluorescence guided surgery and tracer-dose, fact or fiction? Eur J Nucl Med Mol Imaging. 2016;43:1857–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Brouwer OR, Buckle T, Vermeeren L, Klop WM, Balm AJ, van der Poel HG, et al. Comparing the hybrid fluorescent-radioactive tracer indocyanine green-99mTc-nanocolloid with 99mTc-nanocolloid for sentinel node identification: a validation study using lymphoscintigraphy and SPECT/CT. J Nucl Med. 2012;53:1034–40.

    Article  CAS  PubMed  Google Scholar 

  27. Brouwer OR, van den Berg NS, Mathéron HM, van der Poel HG, van Rhijn BW, Bex A, et al. A hybrid radioactive and fluorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye. Eur Urol. 2014;65:600–9.

    Article  CAS  PubMed  Google Scholar 

  28. Verbeek FP, Tummers QR, Rietbergen DD, Peters AA, Schaafsma BE, van de Velde CJ, et al. Sentinel lymph node biopsy in vulvar cancer using combined radioactive and fluorescence guidance. Int J Gynecol Cancer. 2015;25:1086–93.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Altgassen C, Hertel H, Brandstädt A, Köhler C, Dürst M, Schneider A. Multicenter validation study of the sentinel lymph node concept in cervical cancer: AGO Study Group. J Clin Oncol. 2008;26:2943–51.

    Article  PubMed  Google Scholar 

  30. Ruscito I, Gasparri ML, Braicu EI, Bellati F, Raio L, Sehouli J, et al. Sentinel node mapping in cervical and endometrial cancer: indocyanine green versus other conventional dyes – a meta-analysis. Ann Surg Oncol. 2016;23:3749–56.

    Article  PubMed  Google Scholar 

  31. Frontado LM, Brouwer OR, van den Berg NS, Mathéron HM, Vidal-Sicart S, van Leeuwen FW, et al. Added value of the hybrid tracer indocyanine green-99mTc-nanocolloid for sentinel node biopsy in a series of patients with different lymphatic drainage patterns. Rev Esp Med Nucl Imagen Mol. 2013;32:227–33.

    CAS  PubMed  Google Scholar 

  32. van den Berg NS, Brouwer OR, Klop WM, Karakullukcu B, Zuur CL, Tan IB, et al. Concomitant radio- and fluorescence-guided sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity using ICG-(99m)Tc-nanocolloid. Eur J Nucl Med Mol Imaging. 2012;39:1128–36.

    Article  CAS  PubMed  Google Scholar 

  33. van den Berg NS, Simon H, Kleinjan GH, Engelen T, Bunschoten A, Welling MM, et al. First-in-human evaluation of a hybrid modality that allows combined radio- and (near-infrared) fluorescence tracing during surgery. Eur J Nucl Med Mol Imaging. 2015;42:1639–47.

    Article  PubMed  Google Scholar 

  34. Schaafsma BE, van der Vorst JR, Gaarenstroom KN, Peters AA, Verbeek FP, de Kroon CD, et al. Randomized comparison of near-infrared fluorescence lymphatic tracers for sentinel lymph node mapping of cervical cancer. Gynecol Oncol. 2012;127:126–30.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Pandit-Taskar N, Gemignani ML, Lyall A, Larson SM, Barakat RR, Abu Rustum NR. Single photon emission computed tomography SPECT-CT improves sentinel node detection and localization in cervical and uterine malignancy. Gynecol Oncol. 2010;117:59–64.

    Article  PubMed  Google Scholar 

  36. Hoogendam JP, Veldhuis WB, Hobbelink MG, Verheijen RH, van den Bosch MA, Zweemer RP. 99mTc SPECT/CT versus planar lymphoscintigraphy for preoperative sentinel lymph node detection in cervical cancer: a systematic review and metaanalysis. J Nucl Med. 2015;56:675–80.

    Article  PubMed  Google Scholar 

  37. KleinJan GH, van den Berg NS, de Jong J, Wit EM, Thygessen H, Vegt E, et al. Multimodal hybrid imaging agents for sentinel node mapping as a means to (re)connect nuclear medicine to advances made in robot-assisted surgery. Eur J Nucl Med Mol Imaging. 2016;43:1278–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Erika Padilla-Morales for her assistance with English language editing and critical review of the manuscript.

Author information

Authors and Affiliations

  1. Nuclear Medicine Department, Hospital Clínic, Villarroel, 170 08036, Barcelona, Spain

    Pilar Paredes, Sergi Vidal-Sicart, Andrés Tapias, Nuria Sánchez & Francisco Lomeña

  2. Nuclear Medicine Department, Radiopharmacy Unit, Hospital Clínic, Barcelona, Spain

    Francisco Campos & Lorena Carballo

  3. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Pilar Paredes, Sergi Vidal-Sicart, Francisco Campos, Sergio Martínez, Jaume Pahisa, Aureli Torné, Jaume Ordi, Francesc Carmona & Francisco Lomeña

  4. Obstetrics and Neonatology, Hospital Clinic, Institut Clínic of Gynecology, Barcelona, Spain

    Sergio Martínez, Jaume Pahisa, Aureli Torné & Francesc Carmona

  5. Department of Pathology, Hospital Clínic, Barcelona, Spain

    Jaume Ordi

  6. Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Barcelona, Spain

    Jaume Ordi

Authors
  1. Pilar Paredes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sergi Vidal-Sicart
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisco Campos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrés Tapias
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nuria Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sergio Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lorena Carballo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jaume Pahisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aureli Torné
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jaume Ordi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Francesc Carmona
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Francisco Lomeña
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pilar Paredes.

Ethics declarations

Funding

This work was supported by AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca) 2014 SGR grant 279.

Conflict of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paredes, P., Vidal-Sicart, S., Campos, F. et al. Role of ICG-99mTc-nanocolloid for sentinel lymph node detection in cervical cancer: a pilot study. Eur J Nucl Med Mol Imaging 44, 1853–1861 (2017). https://doi.org/10.1007/s00259-017-3706-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-017-3706-4

Keywords

Search

Navigation