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Optimization of Near-Infrared Fluorescent Sentinel Lymph Node Mapping in Cervical Cancer Patients
  1. Joost R. van der Vorst, MD*,
  2. Merlijn Hutteman, MSc*,
  3. Katja N. Gaarenstroom, MD, PhD,
  4. Alexander A. W. Peters, MD, PhD,
  5. J. Sven D. Mieog, MD*,
  6. Boudewijn E. Schaafsma, MD*,
  7. Peter J. K. Kuppen, PhD*,
  8. John V. Frangioni, MD, PhD,§,
  9. Cornelis J. H. van de Velde, MD, PhD* and
  10. Alexander L. Vahrmeijer, MD, PhD*
  1. *Departments of Surgery and
  2. Departments of Gynecology and Obstetrics, Leiden University Medical Center, Leiden, the Netherlands; and
  3. Departments of Department of Radiology and
  4. §Departments of Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  1. Address correspondence and reprint requests to Alexander L. Vahrmeijer, MD, PhD, Albinusdreef 2, 2300 RC Leiden. E-mail: a.l.vahrmeijer{at}


Objective: In early cervical cancer, a total pelvic lymphadenectomy is the standard of care, even though most patients have negative nodes and thus undergo lymphadenectomy unnecessarily. Although the value of sentinel lymph node (SLN) mapping in early-stage cervical cancer has not yet been established, near-infrared (NIR) fluorescence imaging is a promising technique to perform this procedure. Near-infrared fluorescence imaging is based on invisible NIR light and can provide high sensitivity, high-resolution, and real-time image guidance during surgery.

Methods: Clinical trial subjects were 9 consecutive cervical cancer patients undergoing total pelvic lymphadenectomy. Before surgery, 1.6 mL of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected transvaginally and submucosally in 4 quadrants around the tumor. Patients were allocated to 500-, 750-, or 1000-μM ICG:HSA concentration groups. The Mini-FLARE imaging system was used for NIR fluorescence detection and quantitation.

Results: Sentinel lymph nodes were identified in all 9 patients. An average of 3.4 ± 1.2 SLNs was identified per patient. No differences in signal to background of the SLNs between the 500-, 750-, and 1000-μM dose groups were found (P = 0.73). In 2 patients, tumor-positive lymph nodes were found. In both patients, tumor-positive lymph nodes confirmed by pathology were also NIR fluorescent.

Conclusions: This study demonstrated preliminary feasibility to successfully detect SLNs in cervical cancer patients using ICG:HSA and the Mini-FLARE imaging system. When considering safety, cost-effectiveness, and pharmacy preferences, an ICG:HSA concentration of 500 μM was optimal for SLN mapping in cervical cancer patients.

  • Near-infrared fluorescence imaging
  • Image-guided surgery
  • Cervical cancer
  • Sentinel lymph node mapping
  • Indocyanine green

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  • Joost R. van der Vorst, MD, and Merlijn Hutteman, MSc, contributed equally to the study and share first authorship.

  • This work was supported in part by the Nuts Ohra Fund, the Foundation "Maurits and Anna de Kock," and National Institutes of Health grant R01-CA-115296. This work was supported by a Royal Dutch Academy of Arts and Sciences visiting professorship granted to Dr Frangioni.

  • Mini-FLARE technology is owned by Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School. As inventor, Dr Frangioni may someday receive royalties if products are commercialized. Dr Frangioni is the founder and unpaid director of The FLARE Foundation, a nonprofit organization focused on promoting the dissemination of medical imaging technology for research and clinical use. All the other authors have no conflicts of interest to report.

  • Clinical Trial Registration: The Netherlands Trial Register NTR2480