{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:13:02Z","timestamp":1780391582635,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"The Canadian Institutes for Health Research","doi-asserted-by":"publisher","award":["PJT-162433"],"award-info":[{"award-number":["PJT-162433"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fedoruk Center for Nuclear Innovation","award":["PJT-162433"],"award-info":[{"award-number":["PJT-162433"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Novel therapeutic approaches are much needed for the treatment of osteosarcoma. Targeted radionuclide therapy (TRT) and radioimmunotherapy (RIT) are promising approaches that deliver therapeutic radiation precisely to the tumor site. We have previously developed a fully human antibody, named IF3, that binds to insulin-like growth factor 2 receptor (IGF2R). IF3 was used in TRT to effectively inhibit tumor growth in osteosarcoma preclinical models. However, IF3\u2019s relatively short half-life in mice raised the need for improvement. We generated an Fc-engineered version of IF3, termed IF3\u03b4, with amino acid substitutions known to enhance antibody half-life in human serum. In this study, we confirmed the specific binding of IF3\u03b4 to IGF2R with nanomolar affinity, similar to wild-type IF3. Additionally, IF3\u03b4 demonstrated binding to human and mouse neonatal Fc receptors (FcRn), indicating the potential for FcRn-mediated endocytosis and recycling. Biodistribution studies in mice showed a higher accumulation of IF3\u03b4 in the spleen and bone than wild-type IF3, likely attributed to abnormal spleen expression of IGF2R in mice. Therefore, the pharmacokinetics data from mouse xenograft models may not precisely reflect their behavior in canine and human patients. However, the findings suggest both IF3 and IF3\u03b4 as promising options for the RIT of osteosarcoma.<\/jats:p>","DOI":"10.3390\/molecules28155839","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T11:23:03Z","timestamp":1691061783000},"page":"5839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative Molecular Characterization and Pharmacokinetics of IgG1-Fc and Engineered Fc Human Antibody Variants to Insulin-like Growth Factor 2 Receptor (IGF2R)"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9694-7503","authenticated-orcid":false,"given":"Chandra B.","family":"Prabaharan","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabeena","family":"Giri","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J. H.","family":"Allen","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2230-039X","authenticated-orcid":false,"given":"Katrina E. M.","family":"Bato","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0587-0179","authenticated-orcid":false,"given":"Therese R.","family":"Mercado","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9118-0806","authenticated-orcid":false,"given":"Mackenzie E.","family":"Malo","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3854-7776","authenticated-orcid":false,"given":"Jorge L. C.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7300-6479","authenticated-orcid":false,"given":"Ekaterina","family":"Dadachova","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0101-2030","authenticated-orcid":false,"given":"Maruti","family":"Uppalapati","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"ref_1","unstructured":"Vail, D.M., Thamm, D.H., and Liptak, J.M. 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