Competitive Displacement of Serum Protein Binding of Radiopharmaceuticals with Amino Acid Infusion Investigated with N-Isopropyl-p-123I-Iodoamphetamine

When a therapeutic drug is competitively displaced at the bind-ing sites of serum proteins, the free fraction of the drug will be in-creased, with an increase in the manifestation of pharmacologic properties. In the case of molecular imaging probes, total clear-ance and tissue distribution are increased in such circum-stances. The aim of this study was to observe the increase in cerebral accumulation of N-isopropyl-p-123I-iodoamphetamine (123I-IMP) using the protein-binding displacement method with amino acid infusion. Methods: 123I-IMP binding to human serum was investigated and identified. In addition, protein-binding sites and the specific binding sites of human serum albumin (HSA) and a1-acid glycoprotein (AGP) were examined by ultrafiltration. Then, serum-binding sites and the displacement effects of amino acid infusion, including Proteamin 12X Injection and Kidomin, were confirmed in vitro. Subsequently, displacement of 123I-IMP serum protein binding with Proteamin amino acid infusion was tested in monkeys. A scintigraphic study of 123I-IMP in mon-keys loadedwith or without Proteaminwas performed, and time– activity-curves of 123I-IMP brain accumulation in monkeys were evaluated. Results: 123I-IMP was bound to HSA site II and AGP to nearly equal extents. Compared with control conditions, loading with Proteamin and Kidomin markedly increased free fractions of binding site markers for HSA site II (14C-diazepam