Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry

Significance Given the success of combination therapies for the treatment of cancer, the use of bispecific antibodies targeting multiple cancerous molecular pathways is an attractive strategy to enhance the efficacy of current therapeutic paradigms. However, parallel development of companion diagnostic tools is essential for patient identification, stratification, and the early assessment of treatment efficacies. Herein, we describe the generation of a bispecific construct for noninvasive PET imaging of glioblastoma via bioorthogonal click chemistry. The excellent tumor-homing properties displayed by our bispecific probe, which features two antibody fragments simultaneously targeting epidermal growth factor receptor and CD105, demonstrated that our approach is a simple and effective method to generate multispecific targeting agents for noninvasive molecular imaging.