Bispecific antibodies (bAbs) that engage cerebrovascular targets, induce transport across the blood-brain barrier (BBB), and redistribute to secondary targets within the brain parenchyma have the potential to transform the diagnosis and treatment of a wide range of central nervous system disorders. Full understanding of the pharmacokinetics (PK) of these agents, including their potential for delivering cargo into brain parenchymal cells, is a key priority for the development of numerous potential therapeutic applications. To date, the brain PK of bAbs that target transferrin receptor (TfR-1) and CD98 heavy chain (CD98hc) has been characterized using techniques incapable of distinguishing between CNS clearance of intact protein from uptake and catabolism by brain parenchymal cells. Herein, we address this knowledge gap via a comparative radiotracing strategy using two radioisotopes with distinct residualizing properties, iodine-125 (I-125) and zirconium-89 (Zr-89). We first identify reaction conditions for tetravalent chelator modification and Zr-89 radiolabeling that do not adversely affect