Targeted ALPHA therapy with single-domain antibody fragments, a novel cancer treatment

The use of single-domain antibody fragments (sdAb) as vehicles in targeted alpha therapy (TAT) has gained great interest due to their excellent properties. They combine high in vivo affinity and specificity of binding with fast kinetics. This research investigates a novel targeted therapy that combines the α-particle emitter astatine-211 (211At) and the anti-HER2 sdAb 2Rs15d to selectively target HER2pos cancer cells. Two distinctive radiochemical methodologies are investigated using three different coupling reagents. Targeted alpha-particle therapy (TAT) might be a relevant therapeutic strategy to circumvent resistance to conventional therapies in the case of HER2-positive breast and ovarian cancer. Single-domain antibody ragments (sdAb) are promising vehicles for TAT due to their excellent in vivo properties, high target affinity and specificity, fast diffusion and clearance kinetics. This study combines the cytotoxic α-particle emitter bismuth-213 (213Bi) and HER2-targeting sdAbs. Here we describe the development of [213Bi]Bi-DTPA-anti-HER2 sdAb which selectively binds and kills HER2pos SKOV-3 cells.