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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-07-2009 | Original Article

Steroid hormones affect binding of the sigma ligand ¹¹C-SA4503 in tumour cells and tumour-bearing rats

Authors: Anna A. Rybczynska, Philip H. Elsinga, Jurgen W. Sijbesma, Kiichi Ishiwata, Johan R. de Jong, Erik F. de Vries, Rudi A. Dierckx, Aren van Waarde

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2009

Abstract

Purpose

Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist ¹¹C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels.

Methods

¹¹C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone.

Results

Binding of ¹¹C-SA4503 to C6 cells was increased (~50%) upon removal and decreased (~60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC₅₀ progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of ¹¹C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected.

Conclusions

The binding of ¹¹C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids.

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Title: Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats
Authors: Anna A. Rybczynska
Philip H. Elsinga
Jurgen W. Sijbesma
Kiichi Ishiwata
Johan R. de Jong
Erik F. de Vries
Rudi A. Dierckx
Aren van Waarde
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-009-1076-2

At a glance: The STEP trials

Springer Medicine

Steroid hormones affect binding of the sigma ligand ¹¹C-SA4503 in tumour cells and tumour-bearing rats

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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