title: Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide.
abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea. Electronic address: jpark@kirams.re.kr.
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Park
authors.affiliation: 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: Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
authors.forename: In Ok
authors.initials: IO
authors.lastname: Ko
authors.affiliation: Institute of Biomedical Engineering, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Tae-Jeong
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Institute of Biomedical Engineering, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Nuclear Medicine, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
authors.forename: Sang Moo
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
authors.forename: Kyeong Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea. Electronic address: jykim@kirams.re.kr.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000737:chemistry*; D003516:Cycloparaffins / Q000737:chemistry*; D005260:Female; D005682:Gadolinium / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D016023:Integrins / Q000737:chemistry; D007668:Kidney / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D011485:Protein Binding; D001743:Urinary Bladder / Q000378:metabolism
chemical_list: D003287:Contrast Media; D003516:Cycloparaffins; D006571:Heterocyclic Compounds; D016023:Integrins; D009842:Oligopeptides; D009942:Organometallic Compounds; C047981:arginyl-glycyl-aspartic acid; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium
keywords: Contrast agents; Cyclic RGD peptide; Gd-DOTA; MRI; Tumor targeting