[18F]RM273 – A PET probe for the imaging of the sigma2 receptor in brain cancer

The sigma2 receptor (TMEM97) expression correlates well with the Ki67 expression in tumours [1, 2] and therefore represents an attractive marker for the proliferative status. We developed the 18F-labelled radioligand [18F]RM273 for sigma2 receptor imaging in brain tumours.
[18F]RM273 (2-[4-(6-[18F]fluoro-1H-pyrrolo[2,3-b]pyridin-1-yl)butyl]-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinoline) has been obtained by automated synthesis by Cu-mediated oxidative radiofluorination of the aryl boronic acid pinacol ester precursor. Radiometabolite analysis was performed in mouse plasma samples 30 min p.i. The target specificity was investigated by in vitro autoradiographic studies with or without the sigma2 receptor antagonist ISO-1 in rat brain cryosections with a stereotactically implanted F98 glioma [3]. The biodistribution of [18F]RM273 in healthy mice (female, CD1; n = 4; 7.2 ± 1.1 MBq) and the tumour uptake into the F98 glioma (male, Fischer rats; n = 2; 21 and 25 MBq) were investigated by dynamic PET imaging for 60 min (nanoScan®PET-1T MRI, Mediso).
Polar radiometabolites of [18F]RM273 (AM 69 – 233 GBq/μmol, RCY 8%) were detectable in plasma, but not in brain extracts. We determined a 3-times higher density of binding sites in tumour compared to healthy brain in vitro [3]. PET studies revealed a TAC peak value of 1.3 at 2.25 min p.i. followed by a wash out in the brain of healthy mice [3]. In the F98 glioma brain region a two times higher uptake (SUVmean of 0.8–1.3 at 30–60 min p.i.) compared to contralateral was observable. Therefore, [18F]RM273 could potentially be used to determine the proliferative status of brain tumours.
Acknowledgements: This work was supported by the Deutsche Forschungsgemeinschaft (DFG: BR 1360/13-1).
References: [1] Shoghi et al. Plos One 2013, 8: e74188; [2] Yang et al. Molecules 2020, 25 (22): 5439 [3] Moldovan et al. Int. J. Mol. Sci. 2021, 22: 5447