TY - JOUR
T1 - Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer
T2 - novel diagnostic tools for more selective central lymph node compartment dissection
AU - Jonker, Pascal K C
AU - Metman, Madelon J H
AU - Sondorp, Luc H J
AU - Sywak, Mark S
AU - Gill, Anthony J
AU - Jansen, Liesbeth
AU - Links, Thera P
AU - van Diest, Paul J
AU - van Ginhoven, Tessa M
AU - Löwik, Clemens W G M
AU - Nguyen, Anh H
AU - Coppes, Robert P
AU - Robinson, Dominic J
AU - van Dam, Gooitzen M
AU - van Hemel, Bettien M
AU - Fehrmann, Rudolf S N
AU - Kruijff, Schelto
N1 - Funding Information:
This study was financed by a grant from the Dutch Cancer Society from the Koningin Wilhelmina Fonds voor de Nederlandse Kankerbestrijding (KWF) (project number 10851). None of the funding sources was involved in study design, analysis, data interpretation, writing, and submission of this paper.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - Lymph node imaging
KW - Molecular fluorescence-guided imaging
KW - Papillary thyroid cancer
KW - Spectroscopy
UR - https://www.scopus.com/pages/publications/85127692204
U2 - 10.1007/s00259-022-05763-3
DO - 10.1007/s00259-022-05763-3
M3 - Article
C2 - 35389070
SN - 1619-7070
VL - 49
SP - 3557
EP - 3570
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 10
ER -