{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:42:18Z","timestamp":1791513738534,"version":"4.3.4"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T00:00:00Z","timestamp":1757116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T00:00:00Z","timestamp":1757116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Immunotherapy is a mainstay in the treatment of patients with advanced melanoma. Yet, resistance mechanisms exist, and tumour-associated macrophages (TAMs), particularly the M2-like phenotype, are associated with poorer outcomes, with CD206 serving as their specific marker. We present the first human SPECT\/CT study to visualize CD206\u2009+\u2009TAMs in patients undergoing immunotherapy and compare the findings to clinical outcomes (NCT04663126).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Material and methods<\/jats:title>\n            <jats:p>This prospective diagnostic open-label, non-randomized, feasibility study aimed to visualize CD206\u2009+\u2009cells including M2-like TAM in target lesions (T-Lesion) of melanoma patients treated with immunotherapy using [<jats:sup>99m<\/jats:sup>Tc]Tc-Tilmanocept imaging. Patients had dynamic, whole-body planar and SPECT\/CT acquisitions at 1- and 3-h after injection of 350\u00a0MBq\u2009\u00b1\u200910% [<jats:sup>99m<\/jats:sup>Tc]Tc-Tilmanocept. SUV<jats:sub>max\/peak\/mean<\/jats:sub>, MTV and TLA were measured on SPECT\/CT imaging in T-Lesion with ratios to healthy tissues to compare with baseline [<jats:sup>18<\/jats:sup>F]FDG PET\/CT imaging, multispectral immunofluorescence staining findings on lesions\u2019 biopsies, tumour response at three months and follow-up.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Five patients were recruited. T-Lesion uptake on [<jats:sup>99m<\/jats:sup>Tc]Tc-Tilmanocept imaging remained stable at 1- and 3-h post-injection with strong and significant correlations with baseline [<jats:sup>18<\/jats:sup>F]FDG PET\/CT. SUV<jats:sub>max<\/jats:sub> T-Lesion\/ SUV<jats:sub>mean<\/jats:sub> fat-tissue ratio on [<jats:sup>99m<\/jats:sup>Tc]Tc-Tilmanocept SPECT\/CT at 1-h was significantly associated with tumour response at three months (p\u2009=\u20090.005), total cells densities for macrophages and CD8\u2009+\u2009cells on multispectral immunofluorescence staining and poorer outcomes during the follow-up (p\u2009=\u20090.026).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These preliminary pilot data provide the first-in-human proof of concept that CD206-based functional imaging showed measurable signal in tumour lesions in patients with advanced melanoma. If validated it might be useful in reflecting tumour immune status, hence help predicting tumour response to ICI.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00262-025-04127-8","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T07:01:59Z","timestamp":1757142119000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Utility of [99mTc]Tc-tilmanocept, an immunosuppressive macrophage functional imaging agent in melanoma patients receiving checkpoint inhibitor treatment: a feasibility study"],"prefix":"10.1007","volume":"74","author":[{"given":"Sarah","family":"Boughdad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiya","family":"Latifyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margret","family":"Schottelius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Blue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Tissot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Geldhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Costes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John O.","family":"Prior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklaus","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"issue":"23","key":"4127_CR1","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1056\/NEJMoa1406498","volume":"371","author":"A Snyder","year":"2014","unstructured":"Snyder A, Makarov V, Merghoub T et al (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. 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The rest of the authors declare that they have no competing interests relating to this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interests"}},{"value":"This study was done according to the ethical standards defined by the Helsinki declaration and its later amendments (NCT04663126). Our local ethics committee approved this retrospective study with inclusion of all patients that did not explicitly refuse their consent as per the local legislation at the time of the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"298"}}