title: Purification-Free Method for Preparing Technetium-99m-Labeled Multivalent Probes for Enhanced in Vivo Imaging of Saturable Systems.
abstract: 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.
authors.affiliation: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Uehara
authors.affiliation: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.affiliation: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 Japan.
authors.forename: Yota
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 Japan.
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Jen
authors.affiliation: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Arano
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056831:Coordination Complexes; D003952:Diagnostic Imaging; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007553:Isotope Labeling; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008819:Mice, Nude; D015609:Organotechnetium Compounds / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D056831:Coordination Complexes; D039302:Integrin alphaVbeta3; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals