Single-Domain Antibody Theranostics on the Horizon

Single-domain antibody (sdAb) is among the most promising vectors for developing molecular imaging tracers. Several sdAb tracers targeting human epidermal growth factor receptor 2 or programmed death ligand 1 have entered clinical practice. However, radiolabeled single-valent sdAbs generally have high kidney retention, limiting their therapeutic applications. Therefore, engineering strategies such as PEGylation or incorporation of renal cleavable linkers can be adapted to improve pharmacokinetics and reduce kidney retention. In this Focus on Molecular Imaging review, we try to summarize the latest developments in sdAb-derived agents and propose potential strategies that can be used to improve the theranostic value of radiolabeled sdAbs.