Use of a novel receptor-targeted (CD206) radiotracer, 99mTc-tilmanocept, and SPECT/CT for sentinel lymph node detection in oral cavity squamous cell carcinoma: initial institutional report in an ongoing phase 3 study

JAMA Otolaryngol Head Neck Surg. 2013 Sep;139(9):895-902. doi: 10.1001/jamaoto.2013.4239.

Abstract

Importance: Sentinel lymph node biopsy has been proposed as an alternative to up-front elective neck dissection (END) for determination of pathologic nodal status in patients undergoing surgical treatment for oral cavity squamous cell carcinoma (OSCC) with clinically negative neck (cN0). Sentinel lymph node biopsy using current standard tracer agents and imaging adjuncts such as radiolabeled sulfur-colloid and planar lymphoscintigraphy (LS), however, is associated with several drawbacks.

Objective: To assess the preliminary utility of technetium Tc 99m (99mTc)-tilmanocept, a novel molecular imaging agent for sentinel lymph node (SLN) mapping, in OSCC.

Design, setting, and participants: Prospective, nonrandomized, single-arm, part of an ongoing phase 3 clinical trial. Patients had previously untreated, clinically and radiographically node-negative OSCC (T1-4aN0M0) at an academic tertiary referral center.

Interventions: Patients received a single dose of 50 µg 99mTc-tilmanocept injected peritumorally followed by dynamic planar LS and fused single-photon emission computed tomography/computed tomography (SPECT/CT) prior to surgery. Surgical intervention consisted of excision of the primary tumor and radioguided SLN dissection followed by planned END. The excised lymph nodes (SLNs and non-SLNs) underwent histopathologic evaluation for presence of metastatic disease.

Main outcomes and measures: False-negative rate and negative predictive value of SLNB using 99mTc-tilmanocept and comparison of planar LS with SPECT/CT in SLN localization.

Results: Twelve of 20 patients (60%) had metastatic neck disease on pathologic examination. All 12 had at least 1 SLN positive for metastases. No patients had a positive END node who did not have at least 1 positive SLN. These data yield a false-negative rate of 0% and negative predictive value of 100% using 99mTc-tilmanocept in this setting. Dynamic planar LS and SPECT/CT revealed a mean (range) number of hot spots per patient of 2.9 (1-7) and 3.7 (1-12), respectively. Compared with planar LS, SPECT/CT identified additional putative SLNs in 11 of 20 cases (55%).

Conclusions and relevance: The high negative predictive value and low false-negative rate in identification of occult metastases shows 99mTc-tilmanocept to be a promising agent in SLN identification in patients with OSCC. Use of SPECT/CT improves preoperative SLN localization including delineation of SLN locations near the primary tumor when compared with planar LS imaging.

Trial registration: clinicaltrials.gov Identifier: NCT00911326.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / diagnostic imaging*
  • Carcinoma, Squamous Cell / surgery
  • Dextrans*
  • Female
  • Humans
  • Lymph Nodes / diagnostic imaging*
  • Lymph Nodes / surgery
  • Lymphoscintigraphy / methods
  • Male
  • Mannans*
  • Middle Aged
  • Mouth Neoplasms / diagnostic imaging*
  • Mouth Neoplasms / surgery
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prospective Studies
  • Radiopharmaceuticals
  • Sensitivity and Specificity
  • Sentinel Lymph Node Biopsy / methods*
  • Single-Blind Method
  • Technetium Tc 99m Pentetate / analogs & derivatives*
  • Tomography, Emission-Computed, Single-Photon / methods
  • Tomography, X-Ray Computed / methods

Substances

  • Dextrans
  • Mannans
  • Radiopharmaceuticals
  • technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran
  • Technetium Tc 99m Pentetate

Associated data

  • ClinicalTrials.gov/NCT00911326