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Volume 25
Issue 19
10.3390/ijms251910737
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Tumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Mice

by
Thomas Fischer
1,
Felix Dietlein
2,
Detlev Bongartz
3,
Martin Klehr
4,
Beate Zimmermanns
1,
Matthias Schmidt
1,
Angela Mohr
5,
Fabian Mohr
5,
Ferdinand Sudbrock
1,
Philipp Krapf
1,6,
Alexander Drzezga
1,6,7,
Markus Dietlein
1 and
Klaus Schomäcker
1,*
1
Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
2
Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
3
Department of Pediatric Oncology and Hematology, Center for Integrated Oncology, University of Cologne, 50937 Cologne, Germany
4
Department of Pain Management, Helios Hospital, 47805 Krefeld, Germany
5
School of Mathematics and Science, Inorganic Chemistry, University Wuppertal, 42119 Wuppertal, Germany
6
Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany
7
German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Venusberg-Campus 1/99, 53127 Bonn, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(19), 10737; https://doi.org/10.3390/ijms251910737 (registering DOI)
Submission received: 20 August 2024 / Revised: 23 September 2024 / Accepted: 1 October 2024 / Published: 5 October 2024
(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 3.0)
Review Reports Versions Notes

Abstract

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.
Keywords: neuroblastoma; radioimmunotherapy; theranostics; targeted radiotherapy; antibodies neuroblastoma; radioimmunotherapy; theranostics; targeted radiotherapy; antibodies

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MDPI and ACS Style

Fischer, T.; Dietlein, F.; Bongartz, D.; Klehr, M.; Zimmermanns, B.; Schmidt, M.; Mohr, A.; Mohr, F.; Sudbrock, F.; Krapf, P.; et al. Tumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Mice. Int. J. Mol. Sci. 2024, 25, 10737. https://doi.org/10.3390/ijms251910737

AMA Style

Fischer T, Dietlein F, Bongartz D, Klehr M, Zimmermanns B, Schmidt M, Mohr A, Mohr F, Sudbrock F, Krapf P, et al. Tumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Mice. International Journal of Molecular Sciences. 2024; 25(19):10737. https://doi.org/10.3390/ijms251910737

Chicago/Turabian Style

Fischer, Thomas, Felix Dietlein, Detlev Bongartz, Martin Klehr, Beate Zimmermanns, Matthias Schmidt, Angela Mohr, Fabian Mohr, Ferdinand Sudbrock, Philipp Krapf, and et al. 2024. "Tumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Mice" International Journal of Molecular Sciences 25, no. 19: 10737. https://doi.org/10.3390/ijms251910737

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