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.
Highlights
Glioblastoma multiforme (GBM) is the most common primary tumour of the central nervous system
High expression of sigma-1 receptor (sig1R) in different cancer cell lines derived from prostate, breast, colon, small and non-small cell non-small lung cancer,cell brain tumours
We identified the U87-MG cells as suitable for the orthotopic GBM model applied in this study
Summary
Glioblastoma multiforme (GBM) is the most common primary tumour of the central nervous system. Imaging agents for the investigation of the catabolic and anabolic metabolism can detect cancer-specific alterations in high-capacity processes such as glycolysis (by [18 F]FDG), amino acid transport (by [11 C]MET or [18 F]FET), and membrane turnover (by [18 F]FMC) [13,14]. They are currently utilized to improve the clinical management of brain cancer patients. The current development of radiolabelled probes to image e.g., isocitrate dehydrogenase mutations (IDH1R132H) [15], or the glutamate carboxypeptidase II (prostate-specific membrane antigen, PSMA) [16], reflects the interest in preclinical and clinical research on detailed and targeted molecular characterisation of malignancies in the brain, which is a prerequisite to define the role of nuclear medicine imaging for the individualized treatment of patients with GBM [14,17]
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