{"doi":"10.3390/ph16070979","title":"Image-Based Dosimetry in Dogs and Cross-Reactivity with Human Tissues of IGF2R-Targeting Human Antibody","abstract":"Background: Osteosarcoma (OS) represents the most common primary bone tumor in humans and in companion dogs, being practically phenotypically identical. There is a need for effective treatments to extend the survival of patients with OS. Here, we examine the dosimetry in beagle dogs and cross-reactivity with human tissues of a novel human antibody, IF3, that targets the insulin growth factor receptor type 2 (IGF2R), which is overexpressed on OS cells, making it a candidate for radioimmunotherapy of OS. Methods: [89Zr]Zr-DFO-IF3 was injected into three healthy beagle dogs. PET/CT was conducted at 4, 24, 48, and 72 h. RAPID analysis was used to determine the dosimetry of [177Lu]Lu-CHXA”-IF3 for a clinical trial in companion dogs with OS. IF3 antibody was biotinylated, and a multitude of human tissues were assessed with immunohistochemistry. Results: PET/CT revealed that only the liver, bone marrow, and adrenal glands had high uptake. Clearance was initially through renal and hepatobiliary excretion in the first 72 h followed by primarily physical decay. RAPID analysis showed bone marrow to be the dose-limiting organ with a therapeutic range for 177Lu calculated to be 0.487–0.583 GBq. Immunohistochemistry demonstrated the absence of IGF2R expression on the surface of healthy human cells, thus suggesting that radioimmunotherapy with [177Lu]Lu-CHXA”-IF3 will be well tolerated. Conclusions: Image-based dosimetry has defined a safe therapeutic range for canine clinical trials, while immunohistochemistry has suggested that the antibody will not cross-react with healthy human tissues.","journal":"Pharmaceuticals","year":2023,"id":380401,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":886139,"name":"Ohyun Kwon","orcid":"0000-0002-0334-105X","position":1,"is_corresponding":false},{"id":1145460,"name":"Matthew Hutcheson","orcid":"0000-0003-1531-3328","position":2,"is_corresponding":false},{"id":514910,"name":"Joseph J. Grudzinski","orcid":"0000-0002-8799-1649","position":3,"is_corresponding":false},{"id":690943,"name":"Stuart M. Cain","orcid":"0000-0003-1186-0527","position":4,"is_corresponding":false},{"id":1145831,"name":"Frederic A. Cruz","orcid":null,"position":5,"is_corresponding":false},{"id":1145461,"name":"Remitha M. Vinayakamoorthy","orcid":"0000-0002-7526-4065","position":6,"is_corresponding":false},{"id":227588,"name":"Ying Sun","orcid":"0000-0002-2042-6514","position":7,"is_corresponding":false},{"id":1145832,"name":"Lindsay Fairley","orcid":null,"position":8,"is_corresponding":false},{"id":1145833,"name":"Chandra Bose Prabaharan","orcid":null,"position":9,"is_corresponding":false},{"id":1145462,"name":"Ryan Dickinson","orcid":"0000-0002-4031-064X","position":10,"is_corresponding":false},{"id":1145463,"name":"Valerie MacDonald‐Dickinson","orcid":"0009-0005-8255-9194","position":11,"is_corresponding":false},{"id":1145464,"name":"Maruti Uppalapati","orcid":"0000-0003-0101-2030","position":12,"is_corresponding":false},{"id":451106,"name":"Bryan P. Bednarz","orcid":"0000-0002-7467-9816","position":13,"is_corresponding":false},{"id":368608,"name":"Ekaterina Dadachova","orcid":"0000-0001-7300-6479","position":14,"is_corresponding":false},{"id":753288,"name":"Kevin J. H. Allen","orcid":"0000-0001-7046-7317","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T01:17:00.789848Z","pmid":"37513891","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}