Purification-Free Method for Preparing Technetium-99m-Labeled Multivalent Probes for Enhanced in Vivo Imaging of Saturable Systems

Metallic radionuclides provide target-specific radiolabeled probes for molecular imaging in radiochemical yields sufficient for administration to subjects without purification. However, unlabeled ligands in the injectate can compete for targeted molecules with radiolabeled probes, which eventually necessitates postlabeling purification. Herein we describe a "1 to 3" design to circumvent the issue by taking advantage of inherent coordination properties of technetium 99m (Tc-99m). A monovalent RGD ligand possessing an isonitrile as a coordinating moiety (CN-RGD) was reacted with [Tc-99m(CO)(3)(OH2)(3)](+) to prepare [Tc-99m(CO)(3)(CN-RGD)(3)](+) in over 95% radiochemical yields. This complex exhibited higher integrin alpha(v)beta(3) binding affinity than its unlabeled monovalent ligand, primarily due to its multivalency. This compound visualized a murine tumor without removing unlabeled ligands, while a Tc-99m-labeled monovalent probe derived from a monovalent ligand could not. The metal coordination-mediated synthesis of radiolabeled multivalent probes thereby can be a useful approach for preparing ready-to-use target-specific probes labeled with Tc-99m and other metallic radionuclides of interest.