Pretargeted Immuno-PET Enables Monoclonal Antibody Imaging Beyond the Blood-Brain Barrier.

ABSTRACT: Pretargeted PET imaging offers a powerful approach to improve nuclear imaging contrast and reduce systemic radiation exposure, yet its application in the brain has been limited by the blood-brain barrier (BBB). Here, we demonstrate, for the first time, successful pretargeted PET imaging of a brain target enabled by a bispecific antibody engineered for transferrin receptor-mediated BBB transcytosis. By combining this brain shuttle with a novel ¹⁸F-labeled tetrazine, we achieve specific, quantifiable detection of brain-localized Aβ aggregates, validated through PET imaging and histological analysis. This proof-of-concept establishes a versatile, noninvasive imaging platform with broad potential for assessing biologic drug candidates and CNS targets previously considered intractabl

SUBMITTER: Gustavsson T 

PROVIDER: S-EPMC12673582 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature