Actinium-225 macropa complex ([225Ac]Ac-macropa)

Actinium-225 coordinated by the macropa chelator is a radiopharmaceutical complex utilized in Targeted Alpha Therapy (TAT) for the treatment of various cancers (Thiele et al., 2017). Macropa is an 18-membered macrocyclic chelator specifically engineered to bind the large Actinium-225 (Ac-225) cation with high affinity and exceptional kinetic stability, allowing for rapid radiolabeling under mild conditions (Kadassery et al., 2022). This complex is typically conjugated to a targeting moiety, such as a monoclonal antibody or a small molecule ligand, which directs the radioactive payload to specific biomarkers on tumor cells (Palluccio et al., 2024). Once localized, the Ac-225 undergoes a decay chain that releases four high-energy alpha particles, inducing lethal DNA double-strand breaks within the target cells (Wilson et al., 2017). The high stability of the macropa complex is vital for minimizing the release of free actinium and its radioactive daughters, thereby reducing off-target toxicity to the liver and bone (Thiele et al., 2017). This technology represents a significant advancement over traditional chelators like DOTA, particularly for heat-sensitive targeting vectors like antibodies (Kadassery et al., 2022).

Other names

225Ac-macropaActinium-225-macropaMacropa-Ac-225[225Ac]Ac(macropa)+Ac-225-macropa

Targeted Alpha Therapy (TAT); the complex delivers Actinium-225 to tumor cells where it emits high-energy alpha particles that cause lethal DNA double-strand breaks.