Manipulating Pharmacokinetics of Purification-Free Tc-Labeled Bivalent Probes for In Vivo Imaging of Saturable Targets.

The accumulation of Tc-labeled probes targeting saturable systems of the body is hindered by the presence of a large excess of unlabeled ligands needed to ensure high radiochemical yields in a short reaction time. To address the issue, we recently reported a novel concept of a metal-coordination-mediated synthesis of a bivalent Tc-labeled probe from a monovalent ligand using d-penicillamine (Pen) as a chelating molecule and c(RGDfK) as a model targeting device. The Pen-conjugated c(RGDfK) via a hexanoate linkage (Pen-Hx-c(RGDfK)) provided a bivalent [Tc]Tc-[(Pen-Hx-c(RGDfK)) that possessed much higher integrin αβ binding affinity than Pen-Hx-c(RGDfK) and visualized a murine tumor without purification.