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

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 (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
Volume31
Issue number8
DOIs
Publication statusPublished - 2016 Oct 1

Fingerprint

Dimerization
Carboxylic Acids
Positron-Emission Tomography
Pharmacokinetics
Neoplasms
Cyclic Peptides
Chelating Agents
Radioisotopes
Kidney
Control Groups
Peptides
Therapeutics
Growth
1,4,7-triazacyclononane-N,N',N''-triacetic acid

Keywords

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

ASJC Scopus subject areas

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

Cite this

Improved Pharmacokinetics Following PEGylation and Dimerization of a c(RGD-ACH-K) Conjugate Used for Tumor Positron Emission Tomography Imaging. / Lee, Ji Woong; Lee, Yong Jin; Shin, Un Chol; Kim, Suhng Wook; Kim, Byung Il; Lee, Kyo Chul; Kim, Jung Young; Park, Ji Ae.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 31, No. 8, 01.10.2016, p. 295-301.

Research output: Contribution to journalArticle

Lee, Ji Woong ; Lee, Yong Jin ; Shin, Un Chol ; Kim, Suhng Wook ; Kim, Byung Il ; Lee, Kyo Chul ; Kim, Jung Young ; Park, Ji Ae. / Improved Pharmacokinetics Following PEGylation and Dimerization of a c(RGD-ACH-K) Conjugate Used for Tumor Positron Emission Tomography Imaging. In: Cancer Biotherapy and Radiopharmaceuticals. 2016 ; Vol. 31, No. 8. pp. 295-301.
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