Actinium CAR Optimization Preserves 90% Binding, Cuts Liver Uptake
ATNM•Actinium’s evaluation of chelator-to-antibody ratios from 0.7 to 9 found that CAR ≥1.7 enables robust 225Ac labeling while low-CAR (2.5) preserves over 90% antigen binding and boosts internalization. In mice, low-CAR conjugates maintained tumor uptake through 192 hours and cut liver and spleen uptake, widening the therapeutic window.
1. Study Design
Actinium scientists prepared antibody-DOTA conjugates across CAR ranges from 0.7 to 9 and assessed their impact on 225Ac radiolabeling efficiency, antigen binding (91–98% at low CAR), internalization, and biodistribution to identify an optimal chelator-to-antibody ratio.
2. In Vivo Targeting and Safety
Conjugates with CAR ≥1.7 achieved robust 225Ac labeling, while low-CAR (2.5) maintained over 90% antigen binding and enhanced internalization. In mouse models, low-CAR agents sustained tumor uptake through 192 hours and significantly reduced liver and spleen uptake.
3. Pipeline Implications
All optimized conjugates retained radiochemical purity above 97% for seven days, indicating manufacturability. These findings support a wider therapeutic index that may enable higher, safer dosing across Actinium’s radioconjugate pipeline.
