title: New Glucocyclic RGD Dimers for Positron Emission Tomography Imaging of Tumor Integrin Receptors.
abstract: Most studies of radiolabeled arginine-glycine-aspartic acid (RGD) peptides have shown in vitro affinity for integrin ανβ3, allowing for the targeting of receptor-positive tumors in vivo. However, major differences have been found in the pharmacokinetic profiles of different radiolabeled RGD peptide analogs. The purposes of this study were to prepare (64)Cu-DOTA-gluco-E[c(RGDfK)]2 (R8), (64)Cu-NOTA-gluco-E[c(RGDfK)]2 (R9), and (64)Cu-NODAGA-gluco-E[c(RGDfK)]2 (R10) and compare their pharmacokinetics and tumor imaging properties using small-animal positron emission tomography (PET). All three compounds were produced with high specific activity within 10 minutes. The IC50 values were similar for all the substances, and their affinities were greater than that of c(RGDyK). R8, R9, and R10 were stable for 24 hours in human and mouse serums and showed high uptake in U87MG tumors with high tumor-to-blood ratios. Compared to the control, a cyclic RGD peptide dimer without glucosamine, R10, showed low uptake in the liver. Because of their good imaging qualities and improved pharmacokinetics, (64)Cu-labeled dimer RGD conjugates (R8, R9, and R10) may have potential applications as PET radiotracers. R9 (NOTA) with highly in vivo stability consequentially showed an improved PET tumor uptake than R8 (DOTA) or R10 (NODAGA).
authors.affiliation: 1 Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.|2 Department of Integrated Biomedical and Life Science, Korea University , Seoul, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Lee
authors.affiliation: 1 Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Park
authors.affiliation: 1 Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: 1 Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.
authors.forename: Un Chol
authors.initials: UC
authors.lastname: Shin
authors.affiliation: 2 Department of Integrated Biomedical and Life Science, Korea University , Seoul, Republic of Korea.
authors.forename: Suhng Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: 3 Department of Nuclear Medicine, Korea Cancer Center Hospital , Seoul, Republic of Korea.
authors.forename: Byung Il
authors.initials: BI
authors.lastname: Kim
authors.affiliation: 3 Department of Nuclear Medicine, Korea Cancer Center Hospital , Seoul, Republic of Korea.
authors.forename: Sang Moo
authors.initials: SM
authors.lastname: Lim
authors.affiliation: 1 Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.affiliation: 1 Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: 1 Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000032:analysis*; D005260:Female; D005910:Glioma / Q000737:chemistry / Q000000981:diagnostic imaging*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000032:analysis; D064593:Heterografts; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000032:analysis*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000032:analysis*
chemical_list: D003301:Copper Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid; D005944:Glucosamine
keywords: 64Cu; RGD; U87MG; bifunctional chelator; glucosamine; integrin receptor