Comparison of radiobiological effects induced by radiolabeled antibodies in human cancer cells and fungal cells

Abstract

Purpose: Acute myeloid leukemia (AML) is a deadly form of leukemia, and its treatment often leaves patients immunocompromised, making them vulnerable to fungal infections. Radioimmunotherapy (RIT) is explored for both AML and fungal infections. This study compares the radiobiological effects of alpha emitter Actinium-225 (²²⁵Ac) and beta emitter Lutetium-177 (¹⁷⁷Lu)-labeled antibodies on AML and Cryptococcus neoformans cells.

Materials and methods: AML OCI-AML3 and C. neoformans Cap-67 cells were treated with anti-(1-3)-beta-glucan antibody 400-2 and anti-CD33 antibody HuM-195, conjugated to DOTA and radiolabeled with ²²⁵Ac or ¹⁷⁷Lu. Clonogenic survival, γH2A/X staining, and micronuclei assays were conducted. Antibody internalization was assessed by flow cytometry.

Results: Both ²²⁵Ac- and ¹⁷⁷Lu-enabled RIT resulted in decreased clonogenic survival in Cap-67 and OCI-AML3 cells, with Cap-67 recovering more rapidly. DNA double-strand breaks and micronuclei formation revealed DNA damage, with fewer micronuclei in OCI-AML3 cells due to radiation destruction. HuM-195 antibody internalized into OCI-AML3 cells, whereas 400-2 did not internalize into Cap-67 cells.

Conclusions: While both cell lines showed similar responses to ²²⁵Ac- and ¹⁷⁷Lu-enabled RIT, variations were observed based on cellular structure, doubling times and DNA repair mechanisms. This study offers insights for future in vivo research on fungal infections in cancer setting.

Keywords: Actinium-225; Acute myeloid leukemia; Cryptoccocus neoformans; Lutetium-177; radioimmunotherapy.