Combined, yet Separate: cocktails of carriers (not drugs) for α-particle therapy of solid tumors expressing moderate-to-low levels of targetable markers

Alpha-particle radionuclide-antibody conjugates are being clinically evaluated against solid cancers expressing moderate levels of the targeted markers, with promising results. These findings are attributed to the high killing power of alpha-particles in spite of the expected decrease in antibody tumor uptake, that reduces tumor absorbed doses. However, when tumor absorbed doses are reduced, addressing the heterogeneities in delivery of alpha-particles within solid tumors (i.e. enabling uniform irradiation patterns) becomes critical: to maintain efficacy, the fewer alpha-particles delivered within tumors need to traverse/hit as many different cancer cells as possible. This proof-of-concept study describes an approach to complement the antibody- targeted radiotherapy by using a separate carrier to deliver a fraction of the injected radioactivity to tumor regions geographically different than those affected by the antibody; collectively, the two carriers should distribute the alpha-particle emitters, Actinium-225 in particular, more uniformly within tumors maintaining efficacy.