Colabufo Nicola Antonio, Berardi Francesco, Contino Marialessandra, Fazio Ferruccio, Matarrese Mario, Moresco Rosa Maria, Niso Mauro, Perrone Roberto, Tortorella Vincenzo
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, via Orabona 4, 70126 Bari, Italy.
J Pharm Pharmacol. 2005 Nov;57(11):1453-9. doi: 10.1211/jpp.57.11.0011.
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.
σ1和σ2受体已在许多组织中被检测到，并且在来自各种组织的几种肿瘤细胞系中高度表达。σ受体的高表达水平及其在细胞增殖和凋亡中的作用促使人们开发了几种σ配体，以获得用于正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）等体内诊断成像技术的分子探针。植入小鼠体内的EMT-6细胞是通过体内PET评估实体瘤增殖的良好模型。此外，我们开发了σ配体PB167，一种环己基哌嗪衍生物，此前已在标准方案中对其σ2受体亲和力和活性进行了评估。相关结果促使我们验证该化合物是否可以开发为用于体内PET的放射性示踪剂，以便在植入小鼠体内时可视化EMT-6细胞中表达的σ2受体。这种前景被认为是有利的，因为PB167在四氢萘核上带有一个甲氧基取代基，这是进行11C标记的一个容易的位点。这项初步研究的目的既是评估EMT-6细胞中σ1和σ2受体的相对分布，也是验证PB167是否可以开发为用于体内PET的σ2放射性示踪剂。结果表明，σ1和σ2受体在EMT-6细胞中均过表达，并且配体PB167在放射性合成制备方面可以得到积极考虑，以便通过体内PET技术适当地可视化σ2受体，并将它们的存在与肿瘤增殖相关联。
