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 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.
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| http://dx.doi.org/10.1007/s11307-013-0627-x | DOI Listing |
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