Transferrin conjugates of triazacyclononane-based bifunctional NE3TA chelates for PET imaging: Synthesis, Cu-64 radiolabeling, and in vitro and in vivo evaluation

Chi Soo Kang, Ningjie Wu, Yunwei Chen, Xiang Sun, Nilantha Bandara, Dijie Liu, Michael R. Lewis, Buck E. Rogers, Hyun Soon Chong

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Three different polyaminocarboxylate-based bifunctional NE3TA (7-[2-[carboxymethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) chelating agents were synthesized for potential use in copper 64-PET imaging applications. The bifunctional chelates were comparatively evaluated using transferrin (Tf) as a model targeting vector that binds to the transferrin receptor overexpressed in many different cancer cells. The transferrin conjugates of the NE3TA-based bifunctional chelates were evaluated for radiolabeling with 64Cu. In vitro stability and cellular uptake of 64Cu-radiolabeled conjugates were evaluated in human serum and prostate (PC-3) cancer cells, respectively. Among the three NE3TA-Tf conjugates tested, N-NE3TA-Tf was identified as the best conjugate for radiolabeling with 64Cu. N-NE3TA-Tf rapidly bound to 64Cu (> 98% radiolabeling efficiency, 1 min, RT), and 64Cu-N-NE3TA-Tf remained stable in human serum for 2 days and demonstrated high uptake in PC-3 cancer cells. 64Cu-N-NE3TA-Tf was shown to have rapid blood clearance and increasing tumor uptake in PC-3 tumor bearing mice over a 24 h period. This bifunctional chelate presents highly efficient chelation chemistry with 64Cu under mild condition that can be applied for radiolabeling of various tumor-specific biomolecules with 64Cu for potential use in PET imaging applications.

Original languageEnglish
Pages (from-to)60-66
Number of pages7
JournalJournal of Inorganic Biochemistry
Volume154
DOIs
StatePublished - Jan 2016

Keywords

  • Bifunctional chelator
  • Biodistribution
  • Copper 64
  • Radiolabeling
  • Serum stability
  • Transferrin

Fingerprint Dive into the research topics of 'Transferrin conjugates of triazacyclononane-based bifunctional NE3TA chelates for PET imaging: Synthesis, Cu-64 radiolabeling, and in vitro and in vivo evaluation'. Together they form a unique fingerprint.

  • Cite this