title: Improved Pharmacokinetics Following PEGylation and Dimerization of a c(RGD-ACH-K) Conjugate Used for Tumor Positron Emission Tomography Imaging.
abstract: Improving the in vivo pharmacokinetics (PK) of positron emission tomography (PET) radiotracers is of critical importance to tumor diagnosis and therapy. In the case of peptide-based radiotracers, the modification and addition of a linker or spacer functional group often offer faster in vivo pharmacokinetic behavior. In this study, the authors introduced two new PEGlyated dimeric c(RGD-ACH-K) conjugates, in which an aminocyclohexane carboxylic acid (ACH) is inserted into the ring chain of the cyclic RGD peptides, with a common bifunctional chelator (DOTA or NOTA) used for labeling with radiometals (including68Ga and64Cu). The addition of polyethylene glycol (PEG) and dimerization of c(RGD-ACH-K) affected the PK of the renal system and the tumor-targeting ability, relative to unmodified molecule. As a result, both64Cu-DOTA-E[c(RGD-ACH-K)]2(complex 1) and64Cu-NOTA-E[c(RGD-ACH-K)]2(complex 2) exhibited specific tumor-targeting properties relative to tumor-blocking control group, most likely resulting from improved in vivo tumor imaging. The in vivo tumor-to-blood ratio of the64Cu(NOTA) complex shows better PET imaging than that of the64Cu(DOTA) complex, which should lead to improved dosimetry and increased suitability for noninvasive monitoring of tumor growth or tumor-targeted radionuclide therapy.
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: 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: 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
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: Ji-Ae
authors.initials: JA
authors.lastname: Park
mesh_terms: D000598:Amino Acids, Cyclic / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000737:chemistry; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry* / Q000493:pharmacokinetics; D019281:Dimerization; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000598:Amino Acids, Cyclic; D003301:Copper Radioisotopes; D003509:Cyclohexanecarboxylic Acids; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C014966:1-aminocyclohexanecarboxylic acid; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid
keywords: 64Cu; PEGlyation; PET; RGD peptides; dimerization; tumor targeting