CD70-Targeted Radiotheranostics: Now and Future

The cluster of differentiation 70 (CD70), a transmembrane glycoprotein encoded by TNFSF7, is a member of the tumor necrosis factor (TNF) superfamily and serves as the ligand for the co-stimulatory receptor CD27. It is aberrantly overexpressed in various malignancies, including clear cell renal cell carcinoma (ccRCC) and nasopharyngeal carcinoma (NPC). Although CD70-directed radiotheranostics may address key challenges faced by antibody-drug conjugates (ADCs) and chimeric antigen receptor T (CAR-T) therapies, such as drug resistance and tumor penetration barriers, this therapeutic approach remains unexplored in clinical settings. In this review, we highlight the expression of CD70 in normal tissues and organs, as well as in different tumor types, presenting promising results from CD70-targeted immuno-PET/CT imaging in recent clinical trials. Furthermore, we emphasize relevant therapeutic radiopharmaceuticals currently in preclinical or clinical trials, providing a rational roadmap for guiding future development of CD70-targeted radiotheranostics.