Gastric cancer is the 3rd leading cause of cancer mortality worldwide. 2 Lymph node metastasis is common in gastric cancer, and the prognosis of gastric cancer worsens with increasing number of lymph node metastases. 3 Lymph node micrometastases were associated with unfavorable outcome. 4
Esophageal cancer is the 6th leading cause of cancer mortality worldwide. 2 It may metastasize even in the early stage of the disease due to the dense lymph-capillary network. 6 Esophageal Cancer has very poor prognosis, particularly for patients with lymph node metastasis. The presence of micrometastasis was correlated with disease recurrence and poor outcome in esophageal cancer. 7
Patients with ≥33 examined lymph nodes have an additional survival benefit of 19% compared to those with <33 examined lymph nodes.8 This highlights the need for a detection system that improves identification of potential high-risk nodes.
Precise detection of lymph node metastasis is critical for accurate staging and subsequent optimal treatment selection in patients with upper gastrointestinal cancers. FerroTrace® is designed to support clinical decision-making by enabling precise mapping of the lymphatic network and accurate identification of high-risk nodes, providing valuable information to guide treatment planning.
FerroTrace® is a mannose-labelled iron-oxide nanoparticle which is designed to go through the
lymphatic system and be retained in high-risk lymph nodes. FerroTrace® is designed to be optionally used in conjunction with infrared dyes during surgery to enhance intra-operative visualization of lymphtatic network and localization of high-risk lymph nodes. 9
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Fibroblast activation protein (FAP)-targeted iron-oxide nanoparticles have been developed to enhance molecular MRI capabilities and have demonstrated better imaging performance compared with prostate-specific membrane antigen-PET in delineating tumor margins in pre-clinical tumor models. 10
No radiation exposure to the patient or staff
Designed to be used with existing surgical laparoscopic and robotic NIR cameras to identify potential sentinel nodes during surgery
No half-life, eliminates time-sensitive logistical issues seen with radioisotope tracers
Compared with currently available tracers, FerroTrace® is designed to be:
FerroTrace® has been designed to have high specificity to high-risk lymph nodes due to macrophage binding between the CD206 receptor and the tracer’s mannose label. 9,11
FerroTrace® has extented retention in the nodes and therefore eliminates time-sensitive logistical issues associated with radiotracers. Upon delivery, FerroTrace® is visible within minutes with the potential for retention up to 6 months.
Neoadjuvant chemoradiotherapy affects the sensitivity and accuracy of the identification of high-risk lymph nodes using conventional dye or radiotracer techniques during surgery, as radiation damages the lymphatic network.12,13 The extended retention of FerroTrace® enables an added capability of injecting FerroTrace® before neoadjuvant treatment, thereby providing better mapping of high-risk lymph nodes that guides radiation and surgical planning.
Compared with FerroTrace®, blue dyes are non-specific and flow rapidly through multiple levels of lymph nodes. Radiocolloid tracers require careful handling and have a narrow window of use. High concentration of radiocolloid tracers at the injection site may obscure lymph nodes signal when they are located closely to the primary tumor. In contrast, FerroTrace® is easy to use, radiation free with demonstrated efficacy as a lymphatic tracer.9
FerroTrace® has been designed to have high specificity to high-risk lymph nodes due to macrophage binding between the CD206 receptor and the tracer’s mannose label. 9,11
FerroTrace® has extented retention in the nodes and therefore eliminates time-sensitive logistical issues associated with radiotracers. Upon delivery, FerroTrace® is visible within minutes with the potential for retention up to 6 months.
Neoadjuvant chemoradiotherapy affects the sensitivity and accuracy of the identification of high-risk lymph nodes using conventional dye or radiotracer techniques 12,13 during surgery, as radiation damages the lymphatic network. The extended retention of FerroTrace® enables an added capability of performing MRI before neoadjuvant treatment, thereby providing better mapping of high-risk lymph nodes that guides radiation and surgical planning.
Compared with FerroTrace®, indocyanine green and blue dyes are non-specific and flow rapidly through multiple levels of lymph nodes. 9 Radiocolloid tracers require careful handling and have a narrow window of use. High concentration of radiocolloid tracers at the injection site may obscure lymph nodes signal when they are located closely to the primary tumor. 9 In contrast, FerroTrace® is easy to use, radiation free with demonstrated efficacy as a lymphotrophic tracer.
FerroTrace® is currently undergoing clinical trials in upper gastro-intestinal cancer treatment.
A multi-centre clinical trial in collaboration with Flinders Medical Centre and Royal Adelaide Hospital, South Australia and Austin Health and Peter MacCallum Cancer Centre in Melbourne, Australia.
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References
1. National Cancer Institute. Surveillance, Epidemiology and End Results Program. Cancer Stat Facts: Esophageal Cancer. Available from: https://seer.cancer.gov/statfacts/html/esoph.html.
2. Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424.
3. Kinami S, et al. Significance of lymph node metastasis in the treatment of gastric cancer and current challenges in determining the extent of metastasis. Front Oncol 2022;11:806162.
4. Li Y, et al. Lymph node micrometastases is a poor prognostic factor for patients in pN0 gastric cancer: a meta-analysis of observational studies. J Surg Res 2014;191(2):413–22.
5. National Cancer Institute. Surveillance, Epidemiology and End Results Program. Cancer Stat Facts: Stomach Cancer. Available from: https://seer.cancer.gov/statfacts/html/stomach.html.
6. Matsuda S, et al. Lymph node metastatic patterns and the development of multidisciplinary treatment for esophageal cancer. Dis Esophagus 2023;36(4):doad006.
7. Matsumoto M, et al. Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma. Cancer Lett 2000;153(1–2):189–197.
8. Huang L, et al. Importance of Examined Lymph Node Number in Accurate Staging and Enhanced Survival in Resected Gastric Adenocarcinoma-The More, the Better? A Cohort Study of 8,696 Cases From the US and China, 2010-2016. Front Oncol 2021;10:539030.
9. Cousins A, et al. Preclinical evaluation of sentinel node localization in the stomach via mannose- labelled magnetic nanoparticles and indocyanine green. Surg Endosc 2023;37(8):6185–6196.
10. Dmochowska N, et al. Nanoparticles Targeted to Fibroblast Activation Protein Outperform PSMA for MRI Delineation of Primary Prostate Tumors. Small 2023;19(21):e2204956.
11. Krishnan G, et al. Preclinical feasibility of robot-assisted sentinel lymph node biopsy using multi- modality magnetic and fluorescence guidance in the head and neck. Head Neck 2022;44(12):2696–2707.
12. Dabbagh Kakhi VR, et al. Accuracy of sentinel node biopsy in esophageal carcinoma: a systematic review and meta-analysis of the pertinent literature. Surg Today 2014;44(4):607–19.
13. Gabrielson S, et al. Sentinel lymph node imaging with sequential SPECT/CT lymphoscintigraphy before and after neoadjuvant chemoradiotherapy in patients with cancer of the oesophagus or gastro-oesophageal junction – a pilot study. Cancer Imaging 2018;18(1):53.
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