engFischer, ThomasDietlein, FelixDrzezga, AlexanderDietlein, MarkusSchomäcker, KlausBongartz, DetlevKlehr, MartinZimmermanns, BeateSchmidt, MatthiasMohr, AngelaMohr, FabianSudbrock, FerdinandKrapf, PhilippTumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Miceinfo:eu-repo/classification/ddc/540AnimalsNeuroblastoma: pathologyNeuroblastoma: metabolismNeuroblastoma: drug therapyMiceIodine Radioisotopes: adverse effectsCell Line, TumorNeural Cell Adhesion Molecules: metabolismHumansMice, SCIDXenograft Model Antitumor AssaysImmunoconjugates: pharmacologyFemaleAntibodies, Monoclonal: therapeutic useAntibodies, Monoclonal: pharmacology Preliminary studies on a radioactive antibody against the neural cell adhesion molecule (NCAM) demonstrated a significant accumulation of [131I]I-ERIC1 in neuroblastoma tumor cells in mice. This study aims to validate the therapeutic efficacy and potential adverse effects of these radioactive immunoconjugates (RICs) in neuroblastoma-bearing mice. To determine the highest tolerated dose, healthy SCID mice received 1 to 22 MBq of [131I]I-ERIC1, with the survival time measured. Tumor response was evaluated by administering 0.8 to 22 MBq of [131I]I-ERIC1 to neuroblastoma-bearing mice and assessing tumor size and systemic toxicity through body weight, blood counts, and survival. It was observed that doses up to approximately 3 MBq per animal (150 MBq/kg) were well tolerated, whereas higher doses resulted in systemic toxicity and death. The neuroblastomas exhibited a dose-dependent response, with optimal therapeutic efficacy achieved at 1.8-2.5 MBq per animal (90-125 MBq/kg), significantly extending survival by a factor of five. The antibody ERIC1 is a promising vehicle for the transport of beta emitters into NCAM-positive tumor tissue. An optimal dosage of the [131I]I-ERIC1 antibody can be established with a balance of tumor-static effects and adverse effects, resulting in a marked extension of survival time.International journal of molecular sciences 25(19), 10737 (2024). doi:10.3390/ijms251910737 special issue: "Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 3.0"info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionMolecular Diversity Preservation International2024info:eu-repo/semantics/openAccessDEhttps://pub.dzne.de/record/272592https://pub.dzne.de/search?p=id:%22DZNE-2024-01213%22Researchersinfo:eu-repo/semantics/altIdentifier/doi/10.3390/ijms251910737info:eu-repo/semantics/altIdentifier/issn/1422-0067info:eu-repo/semantics/altIdentifier/pmid/pmid:39409066info:eu-repo/semantics/altIdentifier/issn/1661-6596