The clinically used PET radiopaharmaceutical s-(-)[18F]fluspidine offers potential for brain tumor imaging

Overexpression of the sigma-1 receptor (S1R) in various cancers correlates with tumor grade, and drug binding decreases the proliferation of human glioblastoma cell lines. Thus, S1R characterization in glioblastoma could help to better understand its pathophysiology and improve diagnosis or treatment follow-up. Therefore, we aim to evaluate the potential of (S)-(−)-[18F]fluspidine, a highly specific S1R radioligand already applied in clinical studies, to characterize S1R expression in an orthotopic glioblastoma model in mouse with small-animal PET/MRI.
Female nude mice (24-30 g, 8 weeks old) underwent a stereotactic xenograft of U87 cells in the striatum. Healthy female nude mice (25-30 g) were used as control group.
(S)-(-)-[18F]fluspidine (5.6±2.5 MBq; Am: 140±50 GBq/µmol, EOS) was injected intravenously followed by 60 min dynamic PET scans (Mediso nanoScan®). 17 scans were performed and time-activity curves (TAC) from the tumor and the contralateral region were analyzed (PMOD v3.9).
TACs show a comparable profile for healthy mice and the contralateral tumor side. Lower initial uptake values and higher uptake values at the end of the scan were observed in the tumor compared to the contralateral side. Accordingly, the peak-to-end ratio of the tumor region is significantly different from the ratio of the contralateral region (1.65±0.49 vs. 2.19±0.59, p=0.0015)
The PET investigation revealed a significant difference in the pharmacokinetics of (S)-(-)-[18F]fluspidine between the tumor and the contralateral region, probably related to different S1R availability. These first results show the suitability of (S)-(-)-[18F]fluspidine for characterization of U87 S1R status in mice offering hints for brain tumor imaging in human.