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

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)420-433
Number of pages14
JournalMolecular Imaging
Issue number6
StatePublished - Nov 2011
Externally publishedYes

ASJC Scopus subject areas

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


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