Skip to main content
Log in

First-in-human evaluation of a hybrid modality that allows combined radio- and (near-infrared) fluorescence tracing during surgery

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

An Erratum to this article was published on 11 July 2015

Abstract

Purpose

The clinical introduction of the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid, composed of a radioactive and a near-infrared (NIR) fluorescence component, has created the need for surgical (imaging) modalities that allow for simultaneous detection of both signals. This study describes the first-in-human use of a prototype opto-nuclear probe during sentinel node (SN) biopsy using ICG-99mTc-nanocolloid.

Methods

To allow for fluorescence tracing, a derivative of the conventional gamma probe technology was generated in which two optical fibers were integrated to allow for excitation (785 nm) and emission signal collection (> 810 nm). The ability of this opto-nuclear probe to detect the fluorescence signal of the hybrid tracer ICG-99mTc-nanocolloid was firstly determined ex vivo in (non)SNs samples obtained from 41 patients who underwent hybrid tracer-based SN biopsy in the head and neck or urogenital area. In an in vivo proof-of-concept study in nine of these 41 patients, SNs were localized using combined gamma and fluorescence tracing with the opto-nuclear probe. Fluorescence tracing was performed in a similar manner as gamma tracing and under ambient light conditions.

Results

Ex vivo, the gamma tracing option of the opto-nuclear probe correctly identified the SN in all 150 evaluated (non)SN samples. Ex vivo fluorescence tracing in the low-sensitivity mode correctly identified 71.7 % of the samples. This increased to 98.9 % when fluorescence tracing was performed in the high-sensitivity mode. In vivo fluorescence tracing (high-sensitivity mode) accurately identified the SNs in all nine patients (20 SNs evaluated; 100 %).

Conclusion

This study demonstrates the first-in-human evaluation of a hybrid modality capable of detecting both gamma and fluorescence signals during a surgical procedure. Fluorescence tracing could be performed in ambient light.

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

Access this article

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

Similar content being viewed by others

References

  1. van den Berg NS, Buckle T, Kleinjan GH, Klop WM, Horenblas S, van der Poel HG, et al. Hybrid tracers for sentinel node biopsy. Q J Nucl Med Mol Imaging. 2014;58(2):193–206.

    Google Scholar 

  2. Broglie MA, Stoeckli SJ. Relevance of sentinel node procedures in head and neck squamous cell carcinoma. Q J Nucl Med Mol Imaging. 2011;55(5):509–20.

    CAS  PubMed  Google Scholar 

  3. Heuveling DA, van Schie A, Vugts DJ, Hendrikse NH, Yaqub M, Hoekstra OS, et al. Pilot study on the feasibility of PET/CT lymphoscintigraphy with 89Zr-nanocolloidal albumin for sentinel node identification in oral cancer patients. J Nucl Med. 2013;54(4):585–9.

    Article  CAS  PubMed  Google Scholar 

  4. 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(7):1034–40.

    Article  CAS  PubMed  Google Scholar 

  5. van den Berg NS, Brouwer OR, Schaafsma BE, Matheron HM, Klop WM, Balm AJ, et al. Multimodal surgical guidance during sentinel node biopsy for melanoma: combined gamma tracing and fluorescence imaging of the sentinel node through use of the hybrid tracer indocyanine green-Tc-nanocolloid. Radiology. 2015;275(2):530–7.

    Article  Google Scholar 

  6. 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(7):1128–36.

    Article  CAS  PubMed  Google Scholar 

  7. Brouwer OR, van den Berg NS, Matheron 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(3):600–9.

    Article  CAS  PubMed  Google Scholar 

  8. Matheron 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(3):720–5.

    Article  CAS  PubMed  Google Scholar 

  9. Tellier F, Ravelo R, Simon H, Chabrier R, Steibel J, Poulet P. Sentinel lymph node detection by an optical method using scattered photons. Biomed Opt Express. 2010;1(3):902–10.

    Article  PubMed Central  PubMed  Google Scholar 

  10. KleinJan GH, van den Berg NS, Brouwer OR, de Jong J, Acar C, Wit EM, et al. Optimisation of fluorescence guidance during robot-assisted laparoscopic sentinel node biopsy for prostate cancer. Eur Urol. 2014;66(6):991–8.

    Article  PubMed  Google Scholar 

  11. van Leeuwen FWB, Hardwick JCH, van Erkel AR. Luminescence-based imaging approaches in the field of interventional (molecular) imaging. Radiology. 2015. Accepted for publication.

  12. Valdes Olmos RA, Vidal-Sicart S, Giammarile F, Zaknun JJ, Van Leeuwen FW, Mariani G. The GOSTT concept and hybrid mixed/virtual/augmented reality environment radioguided surgery. Q J Nucl Med Mol Imaging. 2014;58(2):207–15.

    CAS  PubMed  Google Scholar 

  13. Engelen T, Winkel BMF, Rietbergen DDD, KleinJan GH, Vidal-Sicart S, Valdés Olmos RA, van den Berg NS, van Leeuwen FWB. The next evolution in radioguided surgery: breast cancer related sentinel node localization using a freehandSPECT-mobile gamma camera combination. A J Nucl Med Mol Imaging. 2015;5(3):233–45.

  14. Brouwer OR, Klop WM, Buckle T, Vermeeren L, van den Brekel MW, Balm AJ, et al. Feasibility of sentinel node biopsy in head and neck melanoma using a hybrid radioactive and fluorescent tracer. Ann Surg Oncol. 2012;19(6):1988–94.

    Article  PubMed Central  PubMed  Google Scholar 

  15. 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(2):291–5.

    Article  CAS  PubMed  Google Scholar 

  16. Mieog JS, Troyan SL, Hutteman M, Donohoe KJ, van der Vorst JR, Stockdale A, et al. Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer. Ann Surg Oncol. 2011;18(9):2483–91.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Bjurlin MA, Gan M, McClintock TR, Volpe A, Borofsky MS, Mottrie A, et al. Near-infrared fluorescence imaging: emerging applications in robotic upper urinary tract surgery. Eur Urol. 2014;65(4):793–801.

    Article  PubMed  Google Scholar 

  18. Ishizawa T, Fukushima N, Shibahara J, Masuda K, Tamura S, Aoki T, et al. Real-time identification of liver cancers by using indocyanine green fluorescent imaging. Cancer. 2009;115(11):2491–504.

    Article  PubMed  Google Scholar 

  19. Zhou Y, Kim YS, Milenic DE, Baidoo KE, Brechbiel MW. In vitro and in vivo analysis of indocyanine green-labeled panitumumab for optical imaging-a cautionary tale. Bioconjug Chem. 2014;25(10):1801–10.

    Article  CAS  PubMed  Google Scholar 

  20. Choi HS, Nasr K, Alyabyev S, Feith D, Lee JH, Kim SH, et al. Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. Angew Chem. 2011;50(28):6258–63.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the entire surgical staff at the The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital for their assistance.

Compliance with ethical standards

Funding

This work was supported in part by grants from the Dutch Cancer Society translational research award program (grant no. PGF 2009–4344), the NWO-STW-VIDI [Netherlands Organisation for Scientific Research-Technical Sciences-Innovational Research Incentives Scheme] (grant no. STW BGT11272), and the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013; grant no. 2012-306890).

Disclosure

The authors each declare that they have no conflicts of interest.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of our institution and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fijs W. B. van Leeuwen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

van den Berg, N.S., Simon, H., Kleinjan, G.H. 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 42, 1639–1647 (2015). https://doi.org/10.1007/s00259-015-3109-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-015-3109-3

Keywords

Navigation