A high-affinity CEA-targeted nanobody for ⁶⁸Ga PET imaging and ¹⁷⁷Lu-based radioisotope therapy: preclinical and first-in-human evaluation.

ABSTRACT: Carcinoembryonic antigen (CEA) is a clinically validated biomarker and therapeutic target in colorectal and other epithelial malignancies, yet current antibody-based approaches are hindered by poor pharmacokinetics, limited tumor penetration, and delayed imaging. To overcome these limitations, we identified a novel high-affinity anti-CEA nanobody (CE-21) with picomolar binding affinity and excellent stability using camelid immune library-based phage display. To ensure homogeneity and maintain antigen recognition, a site-specific conjugation strategy was employed, enabling radiolabeling with gallium-68 for PET/CT imaging or lutetium-177 for radionuclide therapy. [⁶⁸Ga]Ga-CE-21 exhibited rapid renal clearance, low nonspecific uptake, and high tumor-to-background ratios in xenograf

SUBMITTER: Zhang L 

PROVIDER: S-EPMC12645727 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature