University: Institute of Radiopharmaceutical Cancer Research, University Hospital of North Norway (UNN), The Arctic University of Norway, University Hospital Carl Gustav Carus, University Hospital Leipzig, University of Münster
Authors: Magali Toussaint, Winnie Deuther-Conrad, Mathias Kranz, Steffen Fischer, Friedrich-Alexander Ludwig, Tareq A. Juratli, Marianne Patt, Bernhard Wünsch, Gabriele Schackert, Osama Sabri and Peter Brust
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TITLE: Sigma-1 Receptor Positron Emission Tomography: A New Molecular Imaging Approach Using (S)-(−)-[18F]Fluspidine in Glioblastoma
ABSTRACT: Glioblastoma multiforme (GBM) is the most devastating primary brain tumour characterised by infiltrative growth and resistance to therapies.
According to recent research, the sigma-1 receptor (sig1R), an endoplasmic reticulum chaperone protein, is involved in signaling pathways assumed to control the proliferation of cancer cells and thus could serve as candidate for molecular characterisation of GBM. To test this hypothesis, we used the clinically applied sig1R-ligand (S)-(−)-[18F]fluspidine in imaging studies in an orthotopic mouse model of GBM (U87-MG) as well as in human GBM tissue.
A tumour-specific overexpression of sig1R in the U87-MG model was revealed in vitro by autoradiography. The binding parameters demonstrated target-selective binding according to identical KD values in the tumour area and the contralateral side, but a higher density of sig1R in the tumour.
Different kinetic profiles were observed in both areas, with a slower washout in the tumour tissue compared to the contralateral side. The translational relevance of sig1R imaging in oncology is reflected by the autoradiographic detection of tumour-specific expression of sig1R in samples obtained from patients with glioblastoma. Thus, the herein presented data support further research on sig1R in neuro-oncology.