%0 Journal Article
%A Fischer, Thomas
%A Dietlein, Felix
%A Bongartz, Detlev
%A Klehr, Martin
%A Zimmermanns, Beate
%A Schmidt, Matthias
%A Mohr, Angela
%A Mohr, Fabian
%A Sudbrock, Ferdinand
%A Krapf, Philipp
%A Drzezga, Alexander
%A Dietlein, Markus
%A Schomäcker, Klaus
%T Tumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Mice
%J International journal of molecular sciences
%V 25
%N 19
%@ 1422-0067
%C Basel
%I Molecular Diversity Preservation International
%M DZNE-2024-01213
%P 10737
%D 2024
%X  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.
%K Animals
%K Neuroblastoma: pathology
%K Neuroblastoma: metabolism
%K Neuroblastoma: drug therapy
%K Mice
%K Iodine Radioisotopes: adverse effects
%K Cell Line, Tumor
%K Neural Cell Adhesion Molecules: metabolism
%K Humans
%K Mice, SCID
%K Xenograft Model Antitumor Assays
%K Immunoconjugates: pharmacology
%K Female
%K Antibodies, Monoclonal: therapeutic use
%K Antibodies, Monoclonal: pharmacology
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39409066
%2 pmc:PMC11476365
%R 10.3390/ijms251910737
%U https://pub.dzne.de/record/272592