223Ra Induces Transient Functional Bone Marrow Toxicity

• DOI: 10.2967/jnumed.121.263310
• Publication Date: 2022-02-17T21:10:19Z
• Authors: Maria Parlani; Francesco Boccalatte; Anna Yeaton; Feng Wang; Jianhua Zhang; Iannis Aifantis; Eleonora Dondossola
• Keywords: Transient (computer programming)

223Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and currently being tested in variety clinical trials primary cancers to bone. Clinical evaluation hematologic safety showed significantly increased rate neutropenia thrombocytopenia patients, hinting at myelosuppression as side effect. Methods: In this study, we investigated consequences on bone marrow biology by combining flow cytometry, single-cell RNA sequencing, three-dimensional multiphoton microscopy transplantation analyses. Results:223Ra accumulated bones induced zonal radiation damage confined interface, followed replacement impaired areas adipocyte infiltration, monitored 3-dimensional ex vivo. Flow cytometry transcriptomic analyses hematopoietic populations revealed transient, nonspecific 223Ra-mediated cytotoxicity resident populations, including stem, progenitor, mature leukocytes. This toxicity was paralleled significant decrease white blood cells platelets peripheral blood-an effect that overcome within 40 d after treatment. exposure did not impair full reconstitution, suggesting function permanently hampered. Conclusion: Our results provide comprehensive explanation reversible effects exclude long-term myelotoxicity, supporting patients.