225Ac labeled anti-HER2 2Rs15d sdAb as a potential therapeutic for targeted alpha therapy – an in vitro and in vivo evaluation

Human epidermal growth factor receptor type 2 (HER2) over expression cause more aggressive form of cancer, metastatic activity and chemo-resistance. Single-domain antibody fragments (sdAbs) are the smallest antibody-derived fragments with beneficial pharmacokinetic properties for molecular imaging and Targeted Radionuclide Therapy (TRT). Therefore, HER2-targeting sdAbs are very attractive vectors for TRT, especially when labeled with .-particle emitters, due to their small size (~15kDa), nM-range affinity, low immunogenicity, rapid clearance from blood and ease of tumor penetration. The goal of this study was to evaluate the therapeutic potential of the anti-HER2 sdAb 2Rs15d labeled with 225Ac