Immuno-Positron Emission Tomography: Shedding Light on Clinical Antibody Therapy

Monoclonal antibodies (mAbs) have been approved for therapeutic use in a broad range of medical indications, especially in oncology, and are forming the most rapidly expanding category of pharmaceuticals. Although engineered mAb fragments and nontraditional antibody-like scaffolds are receiving increasingly more attention, most of the mAb candidates evaluated in past and ongoing clinical trials are full-length mAbs. Immuno-positron emission tomography (PET), the tracking and quantification of mAbs with PET in vivo at superior imaging quality, is an exciting novel option for better understanding the in vivo behavior and efficacy of mAbs in individual patients. This review focuses on immuno-PET with full-length mAbs, and the associated use of the long-lived positron emitters zirconium-89 (Zr-89) and iodine-124 (I-124). Very recently, crucial achievements have been obtained to allow broad-scale application of Zr-89- and I-124-immuno-PET in clinical mAb development and applications. Zr-89 and I-124 became commercially available worldwide for clinical use. A chelate for facile coupling of Zr-89 to mAbs became commercially available, and generic procedures for labeling of mAbs with Zr-89 and I-124 in a current good manufacturing practice compliant way were established. In this review, critical aspects for the translation of immuno-PET from preclinical investigations to clinical trials will be discussed, as well as the potential clinical applications of immuno-PET. An overview of the results of the first clinical immuno-PET studies will be provided.