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Radioligand therapy can cause changes in blood cell development. This study reveals that [177Lu]Lu-PSMA treatment leads to specific genetic mutations in blood cells, suggesting a selection process rather than damage.

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Area of Science:

  • Oncology
  • Hematology
  • Nuclear Medicine

Background:

  • Radioligand therapy is a precision oncology approach.
  • The long-term effects of radioligand therapy on bone marrow are not fully understood.

Purpose of the Study:

  • To investigate the impact of [177Lu]Lu-PSMA radioligand therapy on bone marrow.
  • To reframe the understanding of bone marrow effects in radioligand therapy.

Main Methods:

  • Analysis of bone marrow following [177Lu]Lu-PSMA administration.
  • Genetic sequencing to identify mutations in hematopoietic cells.

Main Results:

  • [177Lu]Lu-PSMA treatment promotes the emergence and expansion of clonal hematopoiesis.
  • The identified clonal hematopoiesis is enriched for mutations in DNA damage response genes.
  • Bone marrow effects are characterized as treatment-emergent clonal selection.

Conclusions:

  • Bone marrow effects of [177Lu]Lu-PSMA therapy are due to clonal selection, not collateral toxicity.
  • Findings inform biology-guided patient monitoring and theranostics in precision oncology.