{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:24:00Z","timestamp":1792801440085,"version":"4.5.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100015912","name":"Alfred and Annemarie von Sick Grant","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015912","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland","id":[{"id":"https:\/\/ror.org\/05a353079","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EJNMMI Res"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      TEM-1 (tumor endothelial marker-1) is a single-pass transmembrane cell surface glycoprotein expressed at high levels by tumor vasculature and malignant cells. We aimed to perform a preclinical investigation of a novel anti-TEM-1 scFv-Fc fusion antibody, 1C1m-Fc, which was radiolabeled with\n                      <jats:sup>177<\/jats:sup>\n                      Lu for use in soft tissue sarcomas models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      1C1m-Fc was first conjugated to p-SCN-Bn-DOTA using different excess molar ratios and labeled with\n                      <jats:sup>177<\/jats:sup>\n                      Lu. To determine radiolabeled antibody immunoreactivity, Lindmo assays were performed.\n                    <\/jats:p>\n                    <jats:p>The in vivo behavior of [177Lu]Lu-1C1m-Fc was characterized in mice bearing TEM-1 positive (SK-N-AS) and negative (HT-1080) tumors by biodistribution and single-photon emission SPECT\/CT imaging studies. Estimated organ absorbed doses were obtained based on biodistribution results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The DOTA conjugation and the labeling with\n                      <jats:sup>177<\/jats:sup>\n                      Lu were successful with a radiochemical purity of up to 95%. Immunoreactivity after radiolabeling was 86% \u00b1 4%. Biodistribution showed a specific uptake in TEM-1 positive tumor versus liver as critical non-specific healthy organ, and this specificity is correlated to the number of chelates per antibody. A 1.9-fold higher signal at 72\u2009h was observed in SPECT\/CT imaging in TEM-1 positive tumors versus control tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TEM-1 is a promising target that could allow a theranostic approach to soft-tissue sarcoma, and 1C1m-Fc appears to be a suitable targeting candidate. In this study, we observed the influence of the ratio DOTA\/antibody on the biodistribution. The next step will be to investigate the best conjugation to achieve an optimal tumor-to-organ radioactivity ratio and to perform therapy in murine xenograft models as a prelude to future translation in patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13550-020-00685-3","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T08:47:55Z","timestamp":1598863675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["177Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM-1 scFv-Fc fusion protein in soft tissue sarcoma"],"prefix":"10.1186","volume":"10","author":[{"given":"J. A.","family":"Delage","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Faivre-Chauvet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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In particular, all animal experiments in the present study were conducted according to the Swiss federal law on animal experimentation under the cantonal authorization number VD-2993.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"George Coukos has received grants, research support, or is coinvestigator in clinical trials by BMS, Celgene, Boehringer Ingelheim, Roche, Iovance, and Kite. Prof. Coukos has received honoraria for consultations or presentations by Roche, Genentech, BMS, AstraZeneca, Sanofi-Aventis, Nextcure, and GeneosTx. Prof. Coukos has patents in the domain of antibodies and vaccines targeting the tumor vasculature as well as technologies related to T cell expansion and engineering for T cell therapy. George Coukos holds patents around TEM1 antibodies and receives royalties from the University of Pennsylvania regarding technology licensed to Novartis.Julie K. Fierle and Steven M. Dunn hold patents in the domain of antibodies and in particular on the 1C1m antibody used in this study.All other authors declare that they have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"98"}}