Effects of Chelator Modifications on 68Ga-Labeled [Tyr3]Octreotide Conjugates

PurposeSomatostatin 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.ProceduresWe 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.ResultsWith 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.ConclusionsChelator modifications can lead to the altered pharmacokinetics. These results may impact further design considerations for peptide-based imaging agents.