TY  - JOUR
AU  - Fischer, Thomas
AU  - Dietlein, Felix
AU  - Bongartz, Detlev
AU  - Klehr, Martin
AU  - Zimmermanns, Beate
AU  - Schmidt, Matthias
AU  - Mohr, Angela
AU  - Mohr, Fabian
AU  - Sudbrock, Ferdinand
AU  - Krapf, Philipp
AU  - Drzezga, Alexander
AU  - Dietlein, Markus
AU  - Schomäcker, Klaus
TI  - Tumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Mice
JO  - International journal of molecular sciences
VL  - 25
IS  - 19
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DZNE-2024-01213
SP  - 10737
PY  - 2024
AB  -  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.
KW  - Animals
KW  - Neuroblastoma: pathology
KW  - Neuroblastoma: metabolism
KW  - Neuroblastoma: drug therapy
KW  - Mice
KW  - Iodine Radioisotopes: adverse effects
KW  - Cell Line, Tumor
KW  - Neural Cell Adhesion Molecules: metabolism
KW  - Humans
KW  - Mice, SCID
KW  - Xenograft Model Antitumor Assays
KW  - Immunoconjugates: pharmacology
KW  - Female
KW  - Antibodies, Monoclonal: therapeutic use
KW  - Antibodies, Monoclonal: pharmacology
LB  - PUB:(DE-HGF)16
C6  - pmid:39409066
C2  - pmc:PMC11476365
DO  - DOI:10.3390/ijms251910737
UR  - https://pub.dzne.de/record/272592
ER  -