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Sentinel Lymph Node Biopsy in Vulvar Cancer Using Combined Radioactive and Fluorescence Guidance
  1. Floris P.R. Verbeek, MSc*,
  2. Quirijn R.J.G. Tummers, MD*,
  3. Daphne D.D. Rietbergen, MD,
  4. Alexander A.W. Peters, MD, PhD,
  5. Boudewijn E. Schaafsma, MD*,
  6. Cornelis J.H. van de Velde, MD, PhD*,
  7. John V. Frangioni, MD, PhD§,
  8. Fijs W.B. van Leeuwen, PhD,
  9. Katja N. Gaarenstroom, MD, PhD and
  10. Alexander L. Vahrmeijer, MD, PhD*
  1. *Departments of Surgery and
  2. Radiology, Nuclear Medicine Section and Interventional Molecular Imaging Laboratory, and Department of
  3. Gynecology and Obstetrics, Leiden University Medical Center, Leiden, the Netherlands; and
  4. §Department of Radiology and
  5. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  1. Address correspondence and reprint requests to Katja N. Gaarenstroom, MD, PhD, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, the Netherlands. E-mail: k.n.gaarenstroom{at}


Objective Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has recently been introduced to improve the sentinel lymph node (SLN) procedure. Several optical tracers have been successfully tested. However, the optimal tracer formulation is still unknown. This study evaluates the performance of ICG–technetium-99m (99mTc)–nanocolloid in relation to 2 most commonly used ICG-based formulas during SLN biopsy in vulvar cancer.

Methods and Materials Twelve women who planned to undergo SLN biopsy for stage I vulvar cancer were prospectively included. Sentinel lymph node mapping was performed using the dual-modality radioactive and NIR fluorescence tracer ICG–99mTc-nanocolloid. All patients underwent combined SLN localization using NIR fluorescence and the (current) gold standard using blue dye and radioactive guidance.

Results In all 12 patients, at least 1 SLN was detected during surgery. A total of 21 lymph nodes (median 2; range, 1–3) were resected. Median time between skin incision and first SLN detection was 8 (range, 1–22) minutes. All resected SLNs were both radioactive and fluorescent, although only 13 (62%) of 21 SLNs stained blue. Median brightness of exposed SLNs, expressed as signal-to-background ratio, was 5.4 (range, 1.8–11.8). Lymph node metastases were found in 3 patients.

Conclusions Near-infrared fluorescence-guided SLN mapping is feasible and outperforms blue dye staining. Premixing ICG with 99mTc-nanocolloid provides real-time intraoperative imaging of the SN and seems to be the optimal tracer combination in terms of intraoperative detection rate of the SN (100%). Moreover, ICG–99mTc-nanocolloid allows the administration of a 5-times lower injected dose of ICG (compared with ICG and ICG absorbed to human serum albumin) and can be injected up to 20 hours before surgery.

  • Vulvar cancer
  • Image-guided surgery
  • Near-infrared fluorescence
  • Sentinel lymph node mapping
  • Multimodal imaging

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  • F.P.R. Verbeek and Q.R.J.G. Tummers contributed equally to the study and share first authorship.

  • FLARE technology is owned by Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School. J.V. Frangioni has started 3 for-profit companies, Curadel, Curadel ResVet Imaging, and Curadel Surgical Innovations, which have optioned FLARE technology for potential licensing from Beth Israel Deaconess Medical Center. The remaining authors declare no conflicts of interest.