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

  • Nynke S. van den Berg
  • Hervé Simon
  • Gijs H. Kleinjan
  • Thijs Engelen
  • Anton Bunschoten
  • Mick M. Welling
  • Bernard M. Tijink
  • Simon Horenblas
  • Jacques Chambron
  • Fijs W. B. van LeeuwenEmail author
Original Article



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.


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.


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 %).


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.


Radioguided surgery Fluorescence Sentinel node Multimodal Hybrid imaging Gamma probe 



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

Compliance with ethical standards


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).


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.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Nynke S. van den Berg
    • 1
    • 2
  • Hervé Simon
    • 3
  • Gijs H. Kleinjan
    • 1
    • 4
  • Thijs Engelen
    • 1
    • 5
  • Anton Bunschoten
    • 1
  • Mick M. Welling
    • 1
  • Bernard M. Tijink
    • 5
  • Simon Horenblas
    • 2
  • Jacques Chambron
    • 4
  • Fijs W. B. van Leeuwen
    • 1
    • 2
    • 5
    Email author
  1. 1.Interventional Molecular Imaging Laboratory, Department of RadiologyLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of UrologyThe Netherlands Cancer Institute – Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  3. 3.Eurorad S.A.EckbolsheimFrance
  4. 4.Department of Nuclear MedicineThe Netherlands Cancer Institute – Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  5. 5.Department of Head and Neck Surgery and OncologyThe Netherlands Cancer Institute – Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands

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