Tumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Mice
Preliminary studies on a radioactive antibody against the neural cell adhesion molecule (NCAM) demonstrated a significant accumulation of [<sup>131</sup>I]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 [<sup>131</sup>I]I-ERIC1, with the survival time measured. Tumor response was evaluated by administering 0.8 to 22 MBq of [<sup>131</sup>I]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 [<sup>131</sup>I]I-ERIC1 antibody can be established with a balance of tumor-static effects and adverse effects, resulting in a marked extension of survival time.
Authors
- F. Sudbrock
- Klaus Schomäcker (ORCID: https://orcid.org/0000-0003-2636-0058)
- Markus Dietlein (ORCID: https://orcid.org/0000-0003-0992-6099)
- Felix Dietlein (ORCID: https://orcid.org/0000-0002-6651-7155)
- Philipp Krapf (ORCID: https://orcid.org/0000-0003-1671-2443)
- Fabian Mohr (ORCID: https://orcid.org/0000-0001-7272-935X)
- Martin Klehr
- Beate Zimmermanns (ORCID: https://orcid.org/0009-0009-2207-9657)
- Thomas Fischer (ORCID: https://orcid.org/0000-0001-6118-5182)
- Matthias Schmidt (ORCID: https://orcid.org/0000-0002-7519-8897)
- Alexander Drzezga (ORCID: https://orcid.org/0000-0001-6018-716X)
- Angela Mohr
- Detlev Bongartz
Institutions
- Boston Children's Hospital (US)
- Harvard University (US)
- University of Wuppertal (DE)
- Forschungszentrum Jülich (DE)
- University of Cologne (DE)
- German Center for Neurodegenerative Diseases (DE)
- Helios Klinikum Krefeld (DE)
- University Hospital Cologne (DE)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2024-10-05
- DOI
- https://doi.org/10.3390/ijms251910737
- Citations
- 1
- Primary Topic
- Neuroblastoma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.37