【摘要】 奥曲肽等生长抑素类似物（SSA）显像剂DOTATATE、DOTATOC等作为神经内分泌肿瘤（NET）的靶向显像剂对于临床精准诊断具有明显的优势,但是受限于SSTR亚型较多及SSTR阴性等情况,奥曲肽类显像剂存假阴性及假阳性等问题亟待解决。本研究利用靶向肿瘤成纤维成分的NOTA-FAPI-04作为靶向分子,通过运用新型的Al¹⁸F标记方法实现PET显像剂的合成,经Radio-HPLC验证标记率和稳定性。活体显像分别在荷SSTR高表达的IMR-32细胞和荷SSTR低表达的HCT116细胞的模型鼠进行靶向显像和阻断显像。结果显示该方法可实现Al¹⁸F对NOTA-FAPI-04的高效标记,体外稳定性可满足药物使用。实验动物PET显像发现,药物经尾静脉注射30分钟后在皮下瘤肿瘤区域富集,肿瘤摄取率达3.1±0.3%（IMR-32细胞）和3.3±1.1%（HCT116细胞）。Al¹⁸F-NOTA-FAPI-04对于SSA显像具有明确的补充价值,尤其是对SSTR低表达的神经内分泌肿瘤具有明确的检出价值。更多还原

【Abstract】 Octreotide and other somatostatin analogs（SSA） imaging agents, such as DOTATATE and DOTATOC, have obvious advantages for accurate clinical diagnosis as targeted imaging agents for neuroendocrine tumors（NET）. However, due to the limitation of more subtypes of SSTR and negative SSTR, problems such as false negative and false positive of octreotide imaging agents need to be solved. In this study, NOTA-FAPI-04, which targets tumor fibroblast components, was used as the target molecule, and the PET imaging agent was synthesized using a novel Al¹⁸F labeling method. The labeling rate and stability were verified by Radio-HPLC. In vivo imaging was performed on IMR-32 cells with high SSTR expression and HCT116 cells with low SSTR expression, respectively. The results showed that Al¹⁸F could effectively label NOTA-FAPI-04, and the stability of Al¹⁸F could meet the requirements of drug use in vitro. PET imaging of experimental animals showed that the drug was enriched in the subcutaneous tumor region at 30 min after intravenous injection, with tumor uptake rates of 3.1±0.3%（IMR-32 cells） and 3.3±1.1%（HCT116 cells）. Al¹⁸F-NOTA-FAPI-04 has complementary value for SSA imaging, especially for the detection of neuroendocrine tumors with low SSTR expression.更多还原