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Tumoricidal Activity and Side Effects of Radiolabeled Anti-NCAM [131I]-Iodine-ERIC1 in Neuroblastoma-Bearing Mice
Thomas Fischer1, Felix Dietlein2, Detlev Bongartz3
1Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
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.
Insights
Radioactive antibodies targeting neural cell adhesion molecule (NCAM) show promise for neuroblastoma treatment. Optimal dosing of [131I]I-ERIC1 balances tumor control and toxicity, significantly extending survival in mice.
Area of Science:
- Oncology
- Radiopharmaceuticals
- Immunotherapy
Background:
- Radioactive immunoconjugates (RICs) utilize antibodies to deliver radiation to tumors.
- [131I]I-ERIC1 targets the neural cell adhesion molecule (NCAM), often overexpressed in neuroblastoma.
Purpose of the Study:
- To evaluate the therapeutic efficacy and safety of [131I]I-ERIC1 in neuroblastoma-bearing mice.
- To determine the maximum tolerated dose and optimal therapeutic window for [131I]I-ERIC1.
Main Methods:
- Dose-escalation studies in healthy SCID mice to assess toxicity and survival.
- Treatment of neuroblastoma-bearing mice with varying doses of [131I]I-ERIC1.
- Monitoring tumor size, body weight, blood counts, and survival for efficacy and toxicity assessment.
Main Results:
- Doses up to 3 MBq/animal (150 MBq/kg) were well tolerated in healthy mice.
- Higher doses induced systemic toxicity and mortality.
- Optimal therapeutic efficacy observed at 1.8-2.5 MBq/animal (90-125 MBq/kg), extending survival fivefold.
- Neuroblastoma response was dose-dependent.
Conclusions:
- The antibody ERIC1 effectively delivers beta emitters to NCAM-positive neuroblastoma cells.
- [131I]I-ERIC1 demonstrates significant therapeutic potential for neuroblastoma.
- An optimal dosage can be established to balance anti-tumor effects and systemic toxicity, leading to improved survival.
