Wang Qianna, Gan Qianqian, Jiang Yuhao, Xiao Di, Chen Xiaoliang, Zhang Junbo
Key Laboratory of Radiopharmaceuticals of the Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Department of Nuclear Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
ACS Pharmacol Transl Sci. 2023 Oct 11;6(11):1681-1691. doi: 10.1021/acsptsci.3c00146. eCollection 2023 Nov 10.
As the "molecule of the century", 2-deoxy-2-[F]fluoro-d-glucose ([F]FDG) is a radioactive F-labeled glucose derivative with a wide range of applications for positron emission tomography (PET) imaging. Single photon emission computed tomography (SPECT) imaging is widely used, but there is no clinical probe comparable to [F]FDG. In our previous work, [Tc]Tc-CN5DG and [Tc]Tc-CN7DG were successfully developed and achieved high-quality SPECT images. However, they still have the disadvantage of low tumor uptake and/or high uptake by nontarget organs. To develop novel tumor imaging agents with high tumor uptake and excellent tumor/nontarget ratios, in this study, starting from d-glucosamine hydrochloride, four phenyl group-containing isonitrile ligands were designed, synthesized, and radiolabeled with Tc. All the complexes had high radiochemical purity and good hydrophilicity and stability. Biodistribution experiments showed that [Tc]Tc- (i.e., [Tc]Tc-CNMBDG) had the highest tumor uptake and tumor/background ratios among the four probes. In SPECT imaging studies, the tumor detected by [Tc]Tc- was more clearly visible than that of [Tc]Tc-CN7DG because of the inappreciable interference from abdominal uptake. Preliminary clinical studies of [Tc]Tc- have been conducted and successfully showed the lesion location in a patient with non-small-cell lung cancer. In summary, [Tc]Tc- is expected to be a promising tumor SPECT imaging agent.
作为“世纪分子”，2-脱氧-2-[F]氟-D-葡萄糖（[F]FDG）是一种放射性F标记的葡萄糖衍生物，在正电子发射断层扫描（PET）成像中有广泛应用。单光子发射计算机断层扫描（SPECT）成像被广泛使用，但尚无与[F]FDG相当的临床探针。在我们之前的工作中，成功开发了[Tc]Tc-CN5DG和[Tc]Tc-CN7DG，并获得了高质量的SPECT图像。然而，它们仍存在肿瘤摄取低和/或非靶器官摄取高的缺点。为了开发具有高肿瘤摄取和优异肿瘤/非靶比值的新型肿瘤显像剂，本研究从盐酸D-葡糖胺出发，设计、合成了4种含苯基的异腈配体，并进行了Tc放射性标记。所有配合物均具有高放射化学纯度、良好的亲水性和稳定性。生物分布实验表明，[Tc]Tc-（即[Tc]Tc-CNMBDG）在4种探针中具有最高的肿瘤摄取和肿瘤/本底比值。在SPECT成像研究中，由于腹部摄取的干扰不明显，[Tc]Tc-检测到的肿瘤比[Tc]Tc-CN7DG检测到的肿瘤更清晰可见。已对[Tc]Tc-进行了初步临床研究，并成功显示了一名非小细胞肺癌患者的病变位置。总之，[Tc]Tc-有望成为一种有前途的肿瘤SPECT显像剂。
