Improved Pharmacokinetics Following PEGylation and Dimerization of a c(RGD-ACH-K) Conjugate Used for Tumor Positron Emission Tomography Imaging

Ji Woong Lee, Yong Jin Lee, Un Chol Shin, Suhng Wook Kim, Byung Il Kim, Kyo Chul Lee, Jung Young Kim, Ji Ae Park

Research output: Contribution to journalArticle


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 (including 68 Ga and 64 Cu). 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, both 64 Cu-DOTA-E[c(RGD-ACH-K)] 2 (complex 1) and 64 Cu-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 the 64 Cu(NOTA) complex shows better PET imaging than that of the 64 Cu(DOTA) complex, which should lead to improved dosimetry and increased suitability for noninvasive monitoring of tumor growth or tumor-targeted radionuclide therapy.

Original languageEnglish
Pages (from-to)295-301
Number of pages7
JournalCancer Biotherapy and Radiopharmaceuticals
Issue number8
Publication statusPublished - 2016 Oct 1



  • Cu
  • dimerization
  • PEGlyation
  • PET
  • RGD peptides
  • tumor targeting

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

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