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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009741) and NTT (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009108). 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02). In 19 patients, no adverse events related to EMI-137 occurred. 0.13\u00a0mg\/kg EMI-137 was selected as optimal dosage for differentiating NM from normal lymph nodes using MFGI (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and spectroscopy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). MFGI identified 5\/19 levels (26.3%) without NM. EMI-137 binds selectively to MET.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration.<\/jats:title>\n                    <jats:p>NCT03470259.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-022-05763-3","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T02:03:03Z","timestamp":1649296983000},"page":"3557-3570","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["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"],"prefix":"10.1007","volume":"49","author":[{"given":"Pascal K. 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Approval was granted by the Northern Sydney Local Health District Human Research Ethics Committee and the Medical Ethics Committee of the University Medical Center Groningen.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"GMvD is a member of the scientific board of SurgVision BV, founder, shareholder, and CEO of TRACER Europe BV (Groningen, the Netherlands). None of the other authors reported any potential conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}