Cyclic RGD Peptides Incorporating Cycloalkanes: Synthesis and Evaluation as PET Radiotracers for Tumor Imaging

• DOI: 10.1021/ml500135t
• Publication Date: 2014-07-10T15:58:56Z
• Authors: Ji-Ae Park; Yong Jin Lee; Ji Woong Lee; Kyo Chul Lee; Gwang il An; Kyeong Min Kim; Byung il Kim; Tae-Jeong Kim; Jung Young Kim
• Keywords: PET Imaging; Molecular Imaging

Two new bicyclic arginine-glycine-aspartic acid (RGD) peptides, c(RGD-ACP-K) (1a) and c(RGD-ACH-K) (1b), incorporating the aminocyclopentane (ACP) aminocyclohexane (ACH) carboxylic acids, respectively, were synthesized by grafting aminocycloalkane acids onto tetra-peptide RGDK sequence. These peptides their conjugates with DO3A (1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid) (2a–b) exhibit high affinity toward U87MG glioblastoma cells. Their is greater than that exhibited c(RGDyK). Labeling these radiometal 64Cu resulted in radiochemical yields (>97%) of corresponding complexes, abbreviated as c(RGD-ACP-K)-DOTA-64Cu (3a) c(RGD-ACH-K)-DOTA-64Cu (3b). Both 3a 3b are stable for 24 h human mouse serums show tumor uptake, observed positron emission tomography (PET). Blocking experiments preinjection c(RGDyK) confirmed target specificity demonstrated promise PET radiotracers imaging ανβ3-positive tumors.