Absence of somatostatin SST(2) receptor internalization in vivo after intravenous SOM230 application in the AR42J animal tumor model

European Journal of Pharmacology
B WaserJean Claude Reubi

Abstract

Among clinically relevant somatostatin functions, agonist-induced somatostatin receptor subtype 2 (sst(2)) internalization is a potent mechanism for tumor targeting with sst(2) affine radioligands such as octreotide. Since, as opposed to octreotide, the second generation multi-somatostatin analog SOM230 (pasireotide) exhibits strong functional selectivity, it appeared of interest to evaluate its ability to affect sst(2) internalization in vivo. Rats bearing AR42J tumors endogenously expressing somatostatin sst(2) receptors were injected intravenously with SOM230 or with the [Tyr(3), Thr(8)]-octreotide (TATE) analog; they were euthanized at various time points; tumors and pancreas were analyzed by immunohistochemistry for the cellular localization of somatostatin sst(2) receptors. SOM230-induced sst(2) internalization was also evaluated in vitro by immunofluorescence microscopy in AR42J cells. At difference to the efficient in vivo sst(2) internalization triggered by intravenous [Tyr(3), Thr(8)]-octreotide, intravenous SOM230 did not elicit sst(2) internalization: immunohistochemically stained sst(2) in AR42J tumor cells and pancreatic cells were detectable at the cell surface at 2.5min, 10min, 1h, 6h, or 24h after SOM230 inject...Continue Reading

References

Apr 21, 2001·Journal of Medicinal Chemistry·W G RajeswaranD H Coy
Jul 11, 2002·The Journal of Clinical Endocrinology and Metabolism·Pamela U Freda
Oct 31, 2002·Molecular Endocrinology·Gerard ElbergAgnes Schonbrunn
Nov 27, 2002·European Journal of Pharmacology·Jean Claude ReubiHelmut R Mäcke
Aug 16, 2003·Endocrine Reviews·Jean Claude Reubi
Apr 28, 2005·Molecular Pharmacology·Qisheng LiuAgnes Schonbrunn
Oct 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Mihaela GinjJean Claude Reubi
Nov 6, 2007·Molecular and Cellular Endocrinology·Herbert A Schmid
Apr 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mihaela GinjHelmut R Maecke
Nov 13, 2008·The Journal of Clinical Endocrinology and Metabolism·Sarah LescheStefan Schulz
May 16, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Bea WaserJean Claude Reubi

❮ Previous
Next ❯

Citations

May 11, 2012·Neuroendocrinology·Eva Forssell-AronssonHåkan Ahlman
Mar 12, 2013·International Journal of Peptides·Federica BarbieriTullio Florio
Jul 28, 2017·Frontiers in Medicine·Gregory W SeverinUlli Köster
Apr 3, 2021·Frontiers in Endocrinology·Manel Puig-DomingoMónica Marazuela
Oct 19, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Rodney J Hicks
May 17, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Helmut R Maecke, Jean Claude Reubi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.