Effects of Chelator Modifications on 68Ga-Labeled [Tyr 3]Octreotide Conjugates

Academic Article

Abstract

  • Purpose: Somatostatin receptors (SSTR) have been reported as promising targets for imaging agents for cancer. Recently, 68Ga-DOTATOC-based PET imaging has been used successfully for diagnosis and management of SSTR-expressing tumors. The purpose of this study was to evaluate the influence of chelator modifications and charge on 68Ga-labeled peptide conjugates. Procedures: We have synthesized a series of [Tyr3] octreotide conjugates that consisted of different NOTA-based chelators with two to five carboxylate moieties, and compared our results with 68Ga- DOTATOC in both in vitro and in vivo studies. Results: With the exception of 68Ga-1 (three carboxylates), the increased number of carboxylates on the NOTA-based chelators resulted in a reduced binding affinity and internalization. Additionally, the tumor uptake for 68Ga-2 (four carboxylates) and 68Ga-3 (five carboxylates) was reduced compared to that of 68Ga-DOTATOC (three carboxylates) and 68Ga-NO2ATOC (two carboxylates) and 68Ga-1 (three carboxylates) at 2 h p.i. suggesting the presence of an optimal charge for this compound. Conclusions: Chelator modifications can lead to the altered pharmacokinetics. These results may impact further design considerations for peptide-based imaging agents. © 2013 World Molecular Imaging Society.
  • Digital Object Identifier (doi)

    Author List

  • Lin M; Welch MJ; Lapi SE
  • Start Page

  • 606
  • End Page

  • 613
  • Volume

  • 15
  • Issue

  • 5