title: Distribution of sigma receptors in EMT-6 cells: preliminary biological evaluation of PB167 and potential for in-vivo PET.
abstract: Sigma(1) and sigma(2) receptors have been detected in many tissues and are highly expressed in several tumour cell lines from various tissues. The high level of expression observed for sigma receptors and their involvement in cell proliferation and apoptosis has led to the development of several sigma ligands in order to obtain a molecular probe for in-vivo diagnostic imaging techniques such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT). The EMT-6 cells implanted in mice were a good model for evaluating the proliferation of solid tumours by in-vivo PET. Moreover, we developed the sigma ligand PB167, a cyclohexylpiperazine derivative, previously evaluated for sigma(2) receptor affinity and activity in standard protocols. The related results encouraged us to verify if this compound could be developed as a radiotracer for in-vivo PET in order to visualize sigma(2) receptors expressed in EMT-6 cells when implanted in mice. This perspective was thought to be favourable because PB167 bears a methoxy substituent on the tetraline nucleus, an easy point for (11)C labelling. The aims of this preliminary study were both to assess the relative distribution of sigma(1) and sigma(2) receptors in EMT-6 cells and to verify if PB167 could be developed as a sigma(2) radiotracer for in-vivo PET. The results showed that both sigma(1) and sigma(2) receptors were overexpressed in EMT-6 cells and that the ligand PB167 can be positively considered for radiosynthesis preparation in order to suitably visualize sigma(2) receptors by the in-vivo PET technique and correlate their presence to tumour proliferation.
authors.affiliation: Dipartimento Farmaco-Chimico, Università degli Studi di Bari, via Orabona 4, 70126 Bari, Italy. colabufo@farmchim.uniba.it
authors.forename: Nicola Antonio
authors.initials: NA
authors.lastname: Colabufo
authors.forename: Francesco
authors.initials: F
authors.lastname: Berardi
authors.forename: Marialessandra
authors.initials: M
authors.lastname: Contino
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Fazio
authors.forename: Mario
authors.initials: M
authors.lastname: Matarrese
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Moresco
authors.forename: Mauro
authors.initials: M
authors.lastname: Niso
authors.forename: Roberto
authors.initials: R
authors.lastname: Perrone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tortorella
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003510:Cyclohexanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D014316:Tritium; D000097605:Sigma-1 Receptor
chemical_list: D003510:Cyclohexanes; D008024:Ligands; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; D014316:Tritium; D000097605:Sigma-1 Receptor; C515444:PB167; C106107:sigma-2 receptor