Visualization of brain targets with ⁸⁹ Zr‐immuno‐PET using a novel bispecific amyloid ß monoclonal antibody

Recent preclinical and clinical studies in the diagnosis and treatment of Alzheimer Disease (AD) focus on antibody based radioligands and therapeutics by targeting amyloid‐β (Aβ).1 So far, imaging brain targets with bispecific antibodies (using transferrin receptor protein1 as shuttling mechanism) has only been investigated using 124I.2 The disadvantages of 124I limit drastically its clinical potential.3 Therefore, 89Zr is suggested as more suitable positron emitter for labelling of antibodies4, especially in combination with DFO*, the next generation chelator candidate for clinical 89Zr‐immuno‐PET.5 In this study, we evaluated [89Zr]Zr‐DFO*‐NCS labeled bispecific Abeta‐mAb‐scFab8D3 and its mutated analogue Abeta‐mAb‐scFab8D3 T1/2 with faster pharmacokinetics for Aβ imaging and targeting in a preclinical Alzheimer mouse model.