Abstract |
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.
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Authors | 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 |
Journal | Molecular imaging
(Mol Imaging)
Vol. 10
Issue 6
Pg. 420-33
(Dec 2011)
ISSN: 1536-0121 [Electronic] England |
PMID | 22201533
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fluorescent Dyes
- Ligands
- Receptors, sigma
- sigma-2 receptor
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Topics |
- Animals
- Cell Growth Processes
(physiology)
- Cell Line, Tumor
- Cell Tracking
(methods)
- Female
- Fluorescent Dyes
(chemistry, pharmacokinetics)
- Humans
- Leukocytes, Mononuclear
(metabolism)
- Ligands
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Microscopy, Fluorescence, Multiphoton
- Molecular Probe Techniques
- Neoplasms, Experimental
(metabolism)
- Receptors, sigma
(metabolism)
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