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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 ((99m)Tc). A monovalent RGD ligand possessing an isonitrile as a coordinating moiety (CN-RGD) was reacted with [(99m)Tc(CO)3(OH2)3](+) to prepare [(99m)Tc(CO)3(CN-RGD)3](+) in over 95% radiochemical yields. This complex exhibited higher integrin αvβ3 binding affinity than its unlabeled monovalent ligand, primarily due to its multivalency. This compound visualized a murine tumor without removing unlabeled ligands, while a (99m)Tc-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 (99m)Tc and other metallic radionuclides of interest.

This study was undertaken to evaluate the renal radioactivity levels of a newly designed Ga-labeled antibody fragment with a linkage cleaved by enzymes present on the brush border membrane (BBM) lining the lumen of the renal tubule.Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) was conjugated with an antibody Fab fragment through a Met-Val-Lys linkage (Ga-NOTA-MVK-Fab) considering that a Met-Val sequence is a substrate of enzymes on the renal BBM and Ga-NOTA-Met is excreted from the kidney into the urine. The enzymatic recognition of the linkage was evaluated with a low-molecular-weightGa-NOTA-Met-Val-Lys derivative. Biodistribution of radioactivity after injection of Ga-NOTA-MVK-Fab into mice was compared withGa-NOTA-conjugated Fab fragments through a Met-Ile linkage that liberates Ga-NOTA-Met (Ga-NOTA-MI-Fab) or a conventional thiourea linkage (Ga-NOTA-Fab). The MVK linkage remained stable in plasma and was recognized by enzymes on renal BBM to liberate Ga-NOTA-Met. When injected into mice, all threeGa-labeled Fab exhibited similar blood clearance rates and tumor accumulation. Significant differences were observed in the kidney where Ga-NOTA-MVK-Fab registered the lowest renal radioactivity levels from early postinjection time ( < 0.05), followed by Ga-NOTA-MI-Fab, which was well reflected in the SPECT/CT images. These findings indicated that our proposal of liberating a radiolabeled compound to urinary excretion from antibody fragments at the renal BBM to reduce the renal radioactivity levels was applicable to Ga-labeled antibody fragments. Because antibody fragments and constructs share similar metabolic fates in the kidney, the present labeling procedure would also apply to a variety of antibody fragments and constructs of interest..

Radiolabeled anti-TNC Fab' may be useful for the noninvasive diagnosis of myocarditis.