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212Bi-Macroaggregated Albumin Inhibited Mouse Melanoma Growth by Regulating Cell Cycle Checkpoint Markers Without

Satyendra Kumar Singh1,2, Nathan Kauffman1,2,3, Isabelle Maria Lynch1,2,3

  • 1Department of Biomedical Engineering, Michigan State University, East Lansing, Michigan.

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
|April 3, 2025
PubMed
Summary

Bismuth-212 labeled macroaggregated albumin effectively treated mouse melanoma by killing cancer cells and reducing tumor growth without toxicity. This alpha-particle therapy did not promote melanoma repopulation or resistance.

Keywords:
212Biepithelial–mesenchymal transitionmacroaggregated albuminmouse melanomatumor repopulationα-particles

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Area of Science:

  • Oncology
  • Nuclear Medicine
  • Radiotherapy

Background:

  • Alpha-particle emitting radionuclides show promise for cancer treatment.
  • The efficacy of Bismuth-212 (212Bi) for mouse melanoma has not been previously investigated.

Purpose of the Study:

  • To evaluate the efficacy and safety of 212Bi-labeled macroaggregated albumin (MAA) for treating mouse melanoma in vitro and in vivo.

Main Methods:

  • In vitro clonogenic and cell survival assays assessed 212Bi-MAA's melanoma cell-killing ability.
  • Immunoblot assays investigated downstream pathways, radioresistance, and epithelial-to-mesenchymal transition (EMT) markers.
  • In vivo studies involved intratumoral injection of 212Bi-MAA in melanoma-bearing mice to evaluate efficacy, stability, and toxicity.

Main Results:

  • 212Bi-MAA demonstrated effective killing of B16F10 melanoma cells and inhibited their clonogenic capacity.
  • Treatment induced DNA damage and cell death markers, with optimal effects at 3.7 MBq.
  • No significant upregulation of radioresistance, cancer stemness, or EMT markers was observed.
  • In vivo, 212Bi-MAA was retained in tumors, reduced tumor growth, and showed no significant organ toxicity.

Conclusions:

  • 212Bi-MAA is a potent and safe therapeutic agent for mouse melanoma.
  • The treatment effectively inhibits tumor growth without promoting melanoma repopulation or resistance mechanisms.