“Affinity cocktails” of alpha-particle radionuclide antibody-conjugates for solid tumors

Introduction: Antibody-radioconjugates are key to targeted alpha-particle therapies for treating resistant solid tumors [1]. Alpha-particles cause complex DNA damage, making them impervious to resistance [2,3]. However, the limited tumor penetration of strongly binding antibodies combined with alpha-particles’ short range ( < 80μm), non-uniformly irradiate tumors, letting cancer cells escape therapy. Our “affinity-cocktails” comprise: (a) “High-affinity conjugates” that treat cells near vasculature; and (b) “low-affinity conjugates” that penetrate deeper; collectively irradiating the entire tumor.