Sigma-1 Receptor Positron Emission Tomography: A New Molecular Imaging Approach Using ( S)-(-)-[ 18 F]Fluspidine in Glioblastoma

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 (sigmaR1), 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 sigmaR1-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 sigmaR1 in the U87-MG model, revealed in vitro by autoradiography, was confirmed by dynamic PET. 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 sigmaR1 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 sigmaR1 imaging in oncology is reflected by the autoradiographic detection of tumour-specific expression of sigmaR1 in samples obtained from patients with glioblastoma. Thus, the herein presented data support further research on sigmaR1 in neuro-oncology.