Effects of chelator modifications on (68)Ga-labeled [Tyr (3)]octreotide conjugates.

Academic Article


  • PURPOSE: Somatostatin receptors (SSTR) have been reported as promising targets for imaging agents for cancer. Recently, (68)Ga-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 (68)Ga-labeled peptide conjugates. PROCEDURES: We have synthesized a series of [Tyr(3)]octreotide conjugates that consisted of different NOTA-based chelators with two to five carboxylate moieties, and compared our results with (68)Ga-DOTATOC in both in vitro and in vivo studies. RESULTS: With the exception of (68)Ga-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 (68)Ga-2 (four carboxylates) and (68)Ga-3 (five carboxylates) was reduced compared to that of (68)Ga-DOTATOC (three carboxylates) and (68)Ga-NO2ATOC (two carboxylates) and (68)Ga-1 (three carboxylates) at 2┬áh 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.
  • Published In


  • Animals, Cell Line, Tumor, Chelating Agents, Endocytosis, Male, Mice, Mice, Nude, Microscopy, Fluorescence, Octreotide, Organ Specificity, Organometallic Compounds, Rats, Receptors, Somatostatin, Staining and Labeling, Time Factors, Tissue Distribution
  • Digital Object Identifier (doi)

    Author List

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

  • 606
  • End Page

  • 613
  • Volume

  • 15
  • Issue

  • 5