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

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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.

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Acknowledgments

The authors were saddened by the loss of Dr. Michael J. Welch on May 6, 2012. Nicole Fettig, Margaret Morris, Amanda Roth, and Lori Strong are thanked for performing the biodistribution studies. This work was supported by DOE Integrated Research Training Program of Excellence in Radiochemistry (DE-SC0002032).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box.8225, 510 South Kingshighway Blvd, St. Louis, MO, 63110, USA

    Mai Lin, Michael J. Welch & Suzanne E. Lapi

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  1. Mai Lin
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  2. Michael J. Welch
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  3. Suzanne E. Lapi
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Correspondence to Suzanne E. Lapi.

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Lin, M., Welch, M.J. & Lapi, S.E. Effects of Chelator Modifications on 68Ga-Labeled [Tyr3]Octreotide Conjugates. Mol Imaging Biol 15, 606–613 (2013). https://doi.org/10.1007/s11307-013-0627-x

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