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We report on the radiolabeling and preclinical evaluation of the scFv78-Fc, a fully human TEM1-targeting antibody fragment cross-reactive with mouse TEM1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>The scFv78-Fc was conjugated with the chelator<jats:italic>p<\/jats:italic>-SCN-Bn-CHX-A\u201d-DTPA, followed by labeling with indium-111. The number of chelators per molecule was estimated by mass spectrometry. A conventional saturation assay, extrapolated to infinite antigen concentration, was used to determine the immunoreactive fraction of the radioimmunoconjugate. The radiopharmaceutical biodistribution was assessed in immunodeficient mice grafted with Ewing\u2019s sarcoma RD-ES and neuroblastoma SK-N-AS human TEM1-positive tumors. The full biodistribution studies were preceded by a dose-escalation experiment based on the simultaneous administration of the radiopharmaceutical with increasing amounts of unlabeled scFv78-Fc. Radiation dosimetry extrapolations to human adults were obtained from mouse biodistribution data according to established methodologies and additional assumptions concerning the impact of the tumor antigenic sink in the cross-species translation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>[<jats:sup>111<\/jats:sup>In]CHX-DTPA-scFv78-Fc was obtained with a radiochemical purity &gt;\u200998\u00a0% after 1\u00a0h incubation at 42\u00a0\u00b0C and ultrafiltration. It showed good stability in human serum and &gt;\u200970\u00a0% immunoreactive fraction. Biodistribution data acquired in tumor-bearing mice confirmed fast blood clearance and specific tumor targeting in both xenograft models. The radiopharmaceutical off-target uptake was predominantly abdominal. After a theoretical injection of [<jats:sup>111<\/jats:sup>In]CHX-DTPA-scFv78-Fc to the reference person, the organs receiving the highest absorbed dose would be the spleen (0.876\u00a0mGy\/MBq), the liver (0.570\u00a0mGy\/MBq) and the kidneys (0.298\u00a0mGy\/MBq). The total body dose and the effective dose would be 0.058\u00a0mGy\/MBq and 0.116\u00a0mSv\/MBq, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>[<jats:sup>111<\/jats:sup>In]CHX-DTPA-scFv78-Fc binds specifically to endosialin\/TEM1<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. Dosimetry estimates are in the range of other monoclonal antibodies radiolabeled with indium-111. [<jats:sup>111<\/jats:sup>In]CHX-DTPA-scFv78-Fc could be potentially translated into clinic.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s11307-020-01479-8","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T22:57:37Z","timestamp":1580252257000},"page":"979-991","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Preclinical Evaluation and Dosimetry of [111In]CHX-DTPA-scFv78-Fc Targeting Endosialin\/Tumor Endothelial Marker 1 (TEM1)"],"prefix":"10.1007","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4664-1965","authenticated-orcid":false,"given":"Francesco","family":"Cicone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Deno\u00ebl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Gnesin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolo","family":"Riggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melita","family":"Irving","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopinadh","family":"Jakka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklaus","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Viertl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Coukos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John O.","family":"Prior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,28]]},"reference":[{"key":"1479_CR1","doi-asserted-by":"crossref","first-page":"10832","DOI":"10.1073\/pnas.89.22.10832","volume":"89","author":"WJ Rettig","year":"1992","unstructured":"Rettig WJ, Garin-Chesa P, Healey JH, Su SL, Jaffe EA, Old LJ (1992) Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer. 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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. All other authors declare that they have no potential conflict of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All applicable institutional and\/or national guidelines for the care and use of animals were followed. In particular, all animal experiments in the present study were conducted according to the Swiss federal law on animal experimentation under the authorization number VD-2993.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"This article does not contain any studies with human participants performed by any of the authors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}]}}