σ₂ Receptors are promising biomarkers for cancer diagnosis given the relationship between the proliferative status of tumors and their density. With the aim of contributing to the research of σ₂ receptor Positron Emission Tomography (PET) probes, we developed 2-[3-[6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]propyl]-3,4-dihydroisoquinolin-1(2H)-one (3), with optimal σ₂ pharmacological properties and appropriate lipophilicity. Hence, 3 served as the lead compound for the development of a series of dihydroisoquinolinones amenable to radiolabeling. Radiosynthesis for compound 26, which displayed the most appropriate σ₂ profile, was developed and σ₂ specific binding for the corresponding [¹⁸F]-26 was confirmed by in vitro autoradiography on rat brain slices. Despite the excellent in vitro properties, [¹⁸F]-26 could not successfully image σ₂ receptors in the rat brain in vivo, maybe because of its interaction with P-gp. Nevertheless, [¹⁸F]-26 may still be worthy of further investigation for the imaging of σ₂ receptors in peripheral tumors devoid of P-gp overexpression.

σ _2个受体是有希望的给定肿瘤的增殖状态和它们的密度之间的关系的癌症诊断生物标志物。与促进σ的研究的目的₂受体的正电子发射断层扫描（PET）的探针，我们开发了2- [3- [6,7-二甲氧基-3,4-二氢异喹啉-2（ħ） -基]丙基] -3,4-二氢异喹啉-1（2 ħ） -酮（3），具有最佳σ ₂的药理学性质和合适的亲脂性。因此，3用作开发一系列适用于放射性标记的二氢异喹啉酮的先导化合物。放射合成化合物26，其显示最合适的σ ₂轮廓，被开发和σ ₂为相应的[特异性结合¹⁸ F] - 26通过在大鼠脑切片的体外放射自显影证实。尽管在体外性能优异，[ ¹⁸ F] - 26不能成功图像σ _2种在体内大鼠脑受体结合，可能是因为它与P-gp的相互作用。然而，[ ¹⁸ F] - 26可能仍然是值得的成像进一步调查的σ ₂受体在周边的P-gp表达的肿瘤缺乏。