Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer: novel diagnostic tools for more selective central lymph node compartment dissection

  • Eur J Nucl Med Mol Imaging. 2022 Aug;49(10):3557-3570. doi: 10.1007/s00259-022-05763-3.
Pascal K C Jonker  1  2 ,  Madelon J H Metman  1 ,  Luc H J Sondorp  1  3 ,  Mark S Sywak  2 ,  Anthony J Gill  4  5  6 ,  Liesbeth Jansen  1 ,  Thera P Links  7 ,  Paul J van Diest  8  9 ,  Tessa M van Ginhoven  10 ,  Clemens W G M Löwik  11 ,  Anh H Nguyen  12 ,  Robert P Coppes  3  13 ,  Dominic J Robinson  14 ,  Gooitzen M van Dam  15  16 ,  Bettien M van Hemel  17 ,  Rudolf S N Fehrmann  18 ,  Schelto Kruijff  19
Affiliations
  • 1. Department of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, 9713, GZ, the Netherlands.
  • 2. Department of Endocrine Surgery and Surgical Oncology, Royal North Shore Hospital, St Leonards, Australia.
  • 3. Department of Biomedical Sciences of Cell & Systems - Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 4. Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, St Leonards, Australia.
  • 5. Sydney Medical School, University of Sydney, Sydney, Australia.
  • 6. Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, Australia.
  • 7. Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 8. Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • 9. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD, USA.
  • 10. Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • 11. Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands.
  • 12. Department of Pathology, Erasmus MC, Rotterdam, the Netherlands.
  • 13. Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 14. Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • 15. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 16. AxelaRx/TRACER B.V, Groningen, the Netherlands.
  • 17. Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 18. Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 19. Department of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, 9713, GZ, the Netherlands. [email protected].
PMID: 35389070 DOI: 10.1007/s00259-022-05763-3
Abstract

Purpose: Patients undergoing prophylactic central compartment dissection (PCLND) for papillary thyroid Cancer (PTC) are often overtreated. This study aimed to determine if molecular fluorescence-guided imaging (MFGI) and spectroscopy can be useful for detecting PTC nodal metastases (NM) and to identify negative central compartments intraoperatively.

Methods: We used a data-driven prioritization strategy based on transcriptomic profiles of 97 primary PTCs and 80 normal thyroid tissues (NTT) to identify tumor-specific antigens for a clinically available near-infrared fluorescent tracer. Protein expression of the top prioritized antigen was immunohistochemically validated with a tissue microarray containing primary PTC (n = 741) and NTT (n = 108). Staining intensity was correlated with 10-year locoregional recurrence-free survival (LRFS). A phase 1 study (NCT03470259) with EMI-137, targeting MET, was conducted to evaluate safety, optimal dosage for detecting PTC NM with MFGI, feasibility of NM detection with quantitative fiber-optic spectroscopy, and selective binding of EMI-137 for MET.

Results: MET was selected as the most promising antigen. A worse LRFS was observed in patients with positive versus negative MET staining (81.9% versus 93.2%; p = 0.02). In 19 patients, no adverse events related to EMI-137 occurred. 0.13 mg/kg EMI-137 was selected as optimal dosage for differentiating NM from normal lymph nodes using MFGI (p < 0.0001) and spectroscopy (p < 0.0001). MFGI identified 5/19 levels (26.3%) without NM. EMI-137 binds selectively to MET.

Conclusion: MET is overexpressed in PTC and associated with increased locoregional recurrence rates. Perioperative administration of EMI-137 is safe and facilitates NM detection using MFGI and spectroscopy, potentially reducing the number of negative PCLNDs with more than 25%.

Clinical trial registration: NCT03470259.

Keywords
Lymph node imaging; Molecular fluorescence-guided imaging; Papillary thyroid cancer; Spectroscopy.
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