title: Cyclic RGD Peptides Incorporating Cycloalkanes: Synthesis and Evaluation as PET Radiotracers for Tumor Imaging.
abstract: Two new bicyclic arginine-glycine-aspartic acid (RGD) peptides, c(RGD-ACP-K) (1a) and c(RGD-ACH-K) (1b), incorporating the aminocyclopentane (ACP) and aminocyclohexane (ACH) carboxylic acids, respectively, were synthesized by grafting the aminocycloalkane carboxylic acids onto the tetra-peptide RGDK sequence. These peptides and their conjugates with DO3A (1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid) (2a-b) exhibit high affinity toward U87MG glioblastoma cells. Their affinity is greater than that exhibited by c(RGDyK). Labeling these conjugates with radiometal (64)Cu resulted in high radiochemical yields (>97%) of the corresponding complexes, abbreviated as c(RGD-ACP-K)-DOTA-(64)Cu (3a) and c(RGD-ACH-K)-DOTA-(64)Cu (3b). Both 3a and 3b are stable for 24 h in human and mouse serums and show high tumor uptake, as observed by positron emission tomography (PET). Blocking experiments with 3a and 3b by preinjection of c(RGDyK) confirmed their target specificity and demonstrated their promise as PET radiotracers for imaging ανβ3-positive tumors.
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Park
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: Kyeong Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: Byung Il
authors.initials: BI
authors.lastname: Kim
authors.affiliation: Institute of Biomedical Engineering Research, Medical School, Kyungpook National University , Daegu 702-701, Republic of Korea.
authors.forename: Tae-Jeong
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
keywords: Cyclic RGD peptides; PET; integrin receptor; radiotracers; tumor targeting