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Research ArticleOncology

Three-Dimensional Tumor Margin Demarcation Using the Hybrid Tracer Indocyanine Green-99mTc-Nanocolloid: A Proof-of-Concept Study in Tongue Cancer Patients Scheduled for Sentinel Node Biopsy

Philippa Meershoek, Nynke S. van den Berg, Oscar R. Brouwer, H. Jelle Teertstra, Charlotte A.H. Lange, Renato A. Valdés-Olmos, Bernies van der Hiel, Alfons J.M. Balm, W. Martin C. Klop and Fijs W.B. van Leeuwen
Journal of Nuclear Medicine June 2019, 60 (6) 764-769; DOI: https://doi.org/10.2967/jnumed.118.220202
Philippa Meershoek
1Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
2Department of Head-and-Neck Surgery, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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Nynke S. van den Berg
1Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
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Oscar R. Brouwer
1Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
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H. Jelle Teertstra
3Department of Radiology, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; and
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Charlotte A.H. Lange
3Department of Radiology, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; and
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Renato A. Valdés-Olmos
1Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
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Bernies van der Hiel
4Department of Nuclear Medicine, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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Alfons J.M. Balm
2Department of Head-and-Neck Surgery, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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W. Martin C. Klop
2Department of Head-and-Neck Surgery, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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Fijs W.B. van Leeuwen
1Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
2Department of Head-and-Neck Surgery, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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  • FIGURE 1.
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    FIGURE 1.

    Injection method. (A) Standard SN procedure consists of 3–4 superficial injections surrounding tumor. (B) In this study, 12 patients received additional injections, placed deep behind tumor using ultrasound guidance. (C) Radiologist inserts injection needle under ultrasound guidance (red arrows). Nuclear physician then injects ICG-99mTc-nanocolloid via syringe-tubing system (green arrows). (D) Radiologist keeps needle (red arrows) 1–2 mm next to tumor border (yellow area) while nuclear physician injects tracer. (E) Deposit of ICG-99mTc-nanocolloid can be visualized on ultrasound (green area).

  • FIGURE 2.
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    FIGURE 2.

    White light (top) and fluorescence (bottom) imaging during procedure. (A) Preexcision image of tumor. (B) Postexcision image of same tumor. (C) Tumor tissue ex vivo. Stitch in excised tissue marks anterior side (arrow). *Tracer deposit. **Remaining fluorescence signal. ***Tracer deposit surrounding tumor.

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    FIGURE 3.

    Schematic overview of pathologic analysis. (A) Tumor has been marked on H&E-stained slides with indelible ink. Overlay of fluorescence signal is projected onto original image. Distance has been measured between core of fluorescent spots and tumor border as drawn on slides. (B) H&E-stained slides from patient in tumor demarcation group with overlay of fluorescence signal. Fluorescent deposits in excised tumor tissue can be visualized, and distance between fluorescent cores and tumor border was measured.

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    TABLE 1

    Preoperative, Intraoperative, and Pathologic Findings

    ParameterTumor tattooingStandard SN procedureP
    Mean administered dose (MBq) ± SD100.0 ± 34.8 (median, 95.9)78.7 ± 7.3 (median, 79.0)0.059
    Preoperative SN-related hot spots (n)
     Lymphoscintigraphy34 (median per patient, 2)50 (median per patient, 2)0.674
     SPECT/CT34 (median per patient, 2)52 (median per patient, 3)0.836
    Mean intraoperative SN results
     Fluorescent, in vivo4.0 (median, 3)2.7 (median, 2.5)0.192
     Fluorescent, ex vivo3.8 (median, 3.5)3.2 (median, 3)0.365
     Radioactive, in vivo2.9 (median, 3)2.7 (median, 2.5)0.745
     Radioactive, ex vivo4.0 (median, 4)3.0 (median, 3)0.159
    Total excised SNs (n)54 (mean, 4.5; median, 4)60 (mean, 3.2; median, 3)0.090
    Total excised non-SNs (n)11 (mean, 0.9; median, 0.5)9 (mean, 0.5; median, 0)0.215
    Total excised nodes (n)6569
    Pathology (n)
     SNs84830.072
     Non-SNs3270.306
     Total nodes116900.060
     Tumor-positive SNs5 (in 3 patients)5 (in 4 patients)
     Tumor-positive non-SNs1* (in 1 patient)0
     Tumor-positive nodes6 (in 3 patients)5 (in 4 patients)
    Resection status (n)
     R011 (91.7%)19 (100.0%)
     R11 (8.3%)0
    • ↵* In this patient, 1 SN was also found tumor-positive.

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    TABLE 2

    Fluorescence Findings in Excised Tissue

    ParameterData
    Fluorescent spots on tissue section with tumor tissue (n)62
    Fluorescence signal outside tumor tissue (n)58/62 (93.5%)
      Fluorescence signal within   10-mm margin56/58 (96.6%)
      Fluorescence signal outside   10-mm margin2/58 (3.4%)
    Fluorescence signal inside tumor tissue (n)4/62 (6.5%)
    Patients with all fluorescent spots 0–10 mm outside tumor border (n)8/12 (66.7%)
    Patients with fluorescent spot inside tumor (n)4/12 (33.3%)
    Distance from tumor border to fluorescence signal outside tumor (mm)
      Median2.8
      Mean3.2
      Range0.2–10.2 (IQR, 1.3–4.3)
    Distance from tumor border to fluorescence signal inside tumor (mm)
      Median1.2
      Mean1.7
      Range0.2–4.2
    • IQR = interquartile range.

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Journal of Nuclear Medicine: 60 (6)
Journal of Nuclear Medicine
Vol. 60, Issue 6
June 1, 2019
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Three-Dimensional Tumor Margin Demarcation Using the Hybrid Tracer Indocyanine Green-99mTc-Nanocolloid: A Proof-of-Concept Study in Tongue Cancer Patients Scheduled for Sentinel Node Biopsy
Philippa Meershoek, Nynke S. van den Berg, Oscar R. Brouwer, H. Jelle Teertstra, Charlotte A.H. Lange, Renato A. Valdés-Olmos, Bernies van der Hiel, Alfons J.M. Balm, W. Martin C. Klop, Fijs W.B. van Leeuwen
Journal of Nuclear Medicine Jun 2019, 60 (6) 764-769; DOI: 10.2967/jnumed.118.220202

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Three-Dimensional Tumor Margin Demarcation Using the Hybrid Tracer Indocyanine Green-99mTc-Nanocolloid: A Proof-of-Concept Study in Tongue Cancer Patients Scheduled for Sentinel Node Biopsy
Philippa Meershoek, Nynke S. van den Berg, Oscar R. Brouwer, H. Jelle Teertstra, Charlotte A.H. Lange, Renato A. Valdés-Olmos, Bernies van der Hiel, Alfons J.M. Balm, W. Martin C. Klop, Fijs W.B. van Leeuwen
Journal of Nuclear Medicine Jun 2019, 60 (6) 764-769; DOI: 10.2967/jnumed.118.220202
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