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J Nucl Med. 2008; 49 (Supplement 1):131P
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Neurosciences: Basic Science

Emerging Ligands and Targets

Neurosteroid depletion and suppletion affects binding of the sigma ligand 11C-SA4503 in tumor cells and tumor-bearing rats

Anna Rybczynska1, Philip Elsinga1, Jurgen Sijbesma1, Kiichi Ishiwata2, Johan De Jong1, Erik De Vries1, Rudi Dierckx1 and Aren Van Waarde1

1 Nuclear Medicine & Molecular Imaging, University of Groningen Medical Center, Groningen, Netherlands; 2 Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

520

Objectives: Sigma receptors are implied in disorders of memory and cognition, drug addiction, depression and schizophrenia. These binding sites are strongly over-expressed in many tumors. Neuroactive steroids may be endogenous ligands. We examined changes of binding of the ligand 11C-SA4503 in C6 cells and in living rats after steroid depletion and suppletion.

Methods: 11C-SA4503 binding was assessed in C6 monolayers by gamma counting and in pentobarbital-anesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to exogenous steroid (1h or 5 min before tracer addition, respectively). Tumor-bearing male rats were either depleted from neurosteroids by repeated treatment with pentobarbital or injected with progesterone.

Results: Binding of 11C-SA4503 to C6 cells was increased (49%) upon removal and decreased (up to 70%) upon addition of neurosteroid (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > DHEA-sulfate, Kd progesterone 33 nM). Steroid depletion increased the SUV-PET of 11C-SA4503 in rodent brain (27%) and tumor (16%) whereas blood pool radioactivity (AUC) was unaffected. Intraperitoneally administered progesterone reduced only tumor SUV and tumor muscle/contrast (36%).

Conclusions: Cellular binding of 11C-SA4503 is sensitive to neurosteroid competition. Brain uptake of the tracer appears to be particularly sensitive to steroid depletion whereas tumor uptake is affected more by steroid suppletion. Baseline occupancy of sigma receptors by neurosteroids seems to be higher in brain than in periphery.





This Article
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Right arrow Email this article to a friend
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Right arrow Articles by Rybczynska, A.
Right arrow Articles by Van Waarde, A.
PubMed
Right arrow Articles by Rybczynska, A.
Right arrow Articles by Van Waarde, A.