The potent sigma receptor ligand PB167, as a potential PET radiotracer for evaluating the mammary sarcoma in mice

Abstract

σ Receptors have been detected in many tissues and are highly expressed in several tumour cell lines from various tissues. In particular, σ2 receptor subtype is considered to be a potential biomarker for rapid proliferating tumour cells. It was demonstrated that σ2 receptor agonists and σ1 receptor antagonists displayed cytotoxic effect and cell proliferation inhibition in several tumour cell lines such as neuroblastoma, glioma and sarcoma. In the last years several σ ligands have been radiolabelled for obtaining a potential radiotracer suitable in PET technique and among them [11C]-PB28, our cyclohexylpiperazine derivative, [11C]-SA4503, and [ 11C]-I derivative. Recently, we synthesized PB167, a potent σ receptor ligand that bears between the tetralin nucleus and cyclohexylpiperazine moiety a spacer longer than compound PB28. Moreover, PB167 displayed low P app (12 × 10-6 cm/sec) and high clogP (6.19). For this purpose, EMT-6 cells (murine mammary sarcoma) have been selected and subcutaneously implanted in the nape of the neck of mice. In this work we reported both the recognition of σ receptors in EMT-6 cells and PB167 σ receptor affinity evaluation in EMT-6 cells. The biodistribution of [11C]-PB167 will be reported in the next work in the future. ©ARKAT.