Synthesis and evaluation of a ligand targeting the somatostatin-2 receptor for drug delivery to neuroendocrine cancers

Bioorganic & Medicinal Chemistry Letters
Guo Li, Philip S Low

Abstract

Over-expression of the somatostatin-2 (SST2) receptor on plasma membranes of neuroendocrine cancer cells renders it attractive for use in targeting both imaging and therapeutic agents to neuroendocrine tumors. Peptide analogs of somatostatin have dominated this approach to date, however, many peptide analogs are either unstable in vivo or exhibit unwanted non-specific uptake in the liver and kidneys. The purpose of this Letter is to describe the preparation and evaluation of a non-peptide SST2 agonist for use in targeting drugs to neuroendocrine cancers. A non-peptide ligand for the SST2 receptor was identified from the literature as a candidate for development of targeted pharmaceuticals for neuroendocrine tumors, based on its SST2 binding affinity and selectivity for SST2 over other somatostatin receptors. It also offered a multiplicity of possible conjugation sites. Rhodamine conjugates in two positions were used for optical imaging and two compounds were internalized in an SST2 receptor transduced cell line (C6-SST2) via SST2 receptor-mediated endocytosis. Radionuclide conjugates were prepared for in vivo imaging and biodistribution studies in mice. The in vitro binding affinity of (99m)Tc conjugates ranged from a Kd of 37-...Continue Reading

References

Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·L YangA A Patchett
Aug 11, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·V TerpstraT J van Berkel
Aug 16, 2003·Endocrine Reviews·Jean Claude Reubi
Mar 26, 2004·Organic Letters·Juan Jose Díaz-MochónMark Bradley
Jul 21, 2006·Journal of Medicinal Chemistry·Christy Rani R GraceRoland Riek
May 16, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Bea WaserJean Claude Reubi
Dec 10, 2009·Endocrine-related Cancer·Dik J KwekkeboomEric P Krenning
Jul 30, 2010·Journal of Medicinal Chemistry·Alessandra Di CianniMauro Ginanneschi
May 17, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Helmut R Maecke, Jean Claude Reubi
Aug 20, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Julius LeytonEric O Aboagye

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Citations

Sep 14, 2018·Current Protocols in Chemical Biology·Mena Asha KrishnanVenkatesh Chelvam
Jul 12, 2019·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Ananda Kumar KanduluruPhilip S Low

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