Preclinical evaluation of sentinel node localization in the stomach via mannose-labelled magnetic nanoparticles and indocyanine green

Surg Endosc. 2023 Aug;37(8):6185-6196. doi: 10.1007/s00464-023-10099-6. Epub 2023 May 10.

Abstract

Background: Gastrectomy with extended (D2) lymphadenectomy is considered standard of care for gastric cancer to provide the best possible outcomes and pathologic staging. However, D2 gastrectomy is a technically demanding operation and reported to be associated with increased complications and mortality. Application of sentinel lymph node (SLN) concept in gastric cancer has the potential to reduce patient morbidity; however, SLN techniques are not established for gastrectomy, in part due to lack of practical tracers. An effective and convenient tracer with enhanced SLN accumulation is critically needed.

Methods: Mannose-labelled magnetic tracer 'FerroTrace' and fluorescent dye indocyanine green (ICG) were injected laparoscopically into the stomach submucosa of 8 healthy swine under general anaesthesia. Intraoperative fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while preoperative T2-weighted MRI and ex vivo magnetometer probe measurements were used to identify nodes containing FerroTrace. Lymphadenectomy was performed either robotically (n = 2) or via laparotomy (n = 6).

Results: Mixing ICG and FerroTrace ensured concurrence of fluorescent and magnetic signals in SLNs. An initial trial with robotic dissection removed all magnetic LNs (n = 4). In the subsequent laparotomy study that targeted all ICG-LNs based on intraoperative fluorescence imaging, dissection removed an average of 4.7 ± 1.2 fluorescent, and 2.0 ± 1.3 magnetic LNs per animal. Both MRI and magnetometer detected 100% of SLNs (n = 7). FerroTrace demonstrated high specificity to SLNs, which contained 76 ± 30% of total lymphotropic iron, and 88 ± 20 % of the overall magnetometer signal.

Conclusions: Through utilisation of this dual tracer approach, SLNs were identified via preoperative MRI, visualised intraoperatively with fluorescence imaging, and confirmed with a magnetometer. This combination pairs the sensitivity of ICG with SLN-specific FerroTrace and can be used for reliable SLN detection in gastric cancer, with potential applications in neoadjuvant therapy.

Keywords: Dual modality; Gastric cancer; Indocyanine green; MRI; Magnetic nanoparticles; Sentinel lymph node.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coloring Agents
  • Fluorescent Dyes
  • Indocyanine Green
  • Lymph Node Excision
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / pathology
  • Lymph Nodes / surgery
  • Magnetite Nanoparticles*
  • Mannose
  • Sentinel Lymph Node Biopsy / methods
  • Sentinel Lymph Node* / diagnostic imaging
  • Sentinel Lymph Node* / pathology
  • Sentinel Lymph Node* / surgery
  • Stomach Neoplasms* / diagnostic imaging
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / surgery
  • Swine

Substances

  • Indocyanine Green
  • Mannose
  • Magnetite Nanoparticles
  • Coloring Agents
  • Fluorescent Dyes