Alpha radioligands after ADC failure

When ADCs against a surface protein stop working because the payload no longer kills, this idea uses the same protein to deliver radiation instead. Antigen often persists after ADC failure with resistance at the payload level, so a 225Ac- or 177Lu-labelled anti-TROP2 or anti-HER2 antibody would bypass efflux, TOP1 mutations and SLFN11 loss, and crossfire would cover antigen-heterogeneous neighbours. The test is a phase 1 of a HER2 or TROP2 radioimmunoconjugate in ADC-refractory breast cancer, with antigen PET selection and dosimetry. Speculative in maturity, it complements Payload-class switching as the rule for ADC sequencing and draws on radio-antibody and radio-ADC, targeted alpha therapy and TROP2 PET.