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

Int J Mol Sci. 2024 Oct 5;25(19):10737. doi: 10.3390/ijms251910737.

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunoconjugates / pharmacology
  • Iodine Radioisotopes* / adverse effects
  • Mice
  • Mice, SCID
  • Neural Cell Adhesion Molecules / metabolism
  • Neuroblastoma* / drug therapy
  • Neuroblastoma* / metabolism
  • Neuroblastoma* / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Iodine Radioisotopes
  • Neural Cell Adhesion Molecules
  • Immunoconjugates
  • Iodine-131
  • Antibodies, Monoclonal

Grants and funding

This research received no external funding.