Characterization and evaluation of two novel fluorescent sigma-2 receptor ligands as proliferation probes

Chenbo Zeng, Suwanna Vangveravong, Lynne A. Jones, Krzysztof Hyrc, Katherine C. Chang, Jinbin Xu, Justin M. Rothfuss, Mark P. Goldberg, Richard S. Hotchkiss, Robert H. Mach

Resultado de la investigación: Articlerevisión exhaustiva

35 Citas (Scopus)


We synthesized and characterized two novel fluorescent sigma-2 receptor selective ligands, SW120 and SW116, and evaluated these ligands as potential probes for imaging cell proliferation. Both ligands are highly selective for sigma-2 receptors versus sigma-1 receptors. SW120 and SW116 were internalized into MDA-MB-435 cells, and 50% of the maximum fluorescent intensity was reached in 11 and 24 minutes, respectively. In vitro studies showed that 50% of SW120 or SW116 washed out of cells in 1 hour. The internalization of SW120 was reduced ≈30% by phenylarsine oxide, an inhibitor of endocytosis, suggesting that sigma-2 ligands are internalized, in part, by an endocytotic pathway. Subcellular localization studies using confocal and two-photon microscopy showed that SW120 and SW116 partially colocalized with fluorescent markers of mitochondria, endoplasmic reticulum, lysosomes, and the plasma membrane, suggesting that sigma-2 receptors localized to the cytoplasmic organelles and plasma membrane. SW120 did not colocalize with the nuclear dye 4',6-diamidino-2-phenylindole. In vivo studies showed that the uptake of SW120 in solid tumors and peripheral blood mononuclear cells of mice positively correlated with the expression level of the cell proliferation marker Ki-67, suggesting that sigma-2 fluorescent probes may be used to image cell proliferation in mice.

Idioma originalEnglish (US)
Páginas (desde-hasta)420-433
Número de páginas14
PublicaciónMolecular Imaging
EstadoPublished - nov. 2011
Publicado de forma externa

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics


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