Jiang Yuhao, Fang Si'an, Feng Junhong, Ruan Qing, Zhang Junbo
Key Laboratory of Radiopharmaceuticals of Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Product Administration), College of Chemistry, Beijing Normal University, Beijing 100875, China.
Mol Pharm. 2023 Jan 2;20(1):630-640. doi: 10.1021/acs.molpharmaceut.2c00830. Epub 2022 Nov 18.
To seek a novel Tc-labeled quinolone derivative for bacterial infection SPECT imaging that aims to lower nontarget organ uptake, a novel norfloxacin 6-hydrazinoicotinamide (HYNIC) derivative (HYNICNF) was designed and synthesized. It was radiolabeled with different coligands, such as tricine, trisodium triphenylphosphine-3,3',3″-trisulfonate (TPPTS), sodium triphenylphosphine-3-monosulfonate (TPPMS), and ethylenediamine-,'-diacetic acid (EDDA), to obtain three Tc-labeled norfloxacin HYNIC complexes, namely, [Tc]Tc-tricine-TPPTS-HYNICNF, [Tc]Tc-tricine-TPPMS-HYNICNF, and [Tc]Tc-EDDA-HYNICNF. These complexes were purified (RCP > 95%) and evaluated and for targeting bacteria. All three complexes are hydrophilic, maintain good stability, and specifically bind . The biodistribution in mice with bacterial infection demonstrated that [Tc]Tc-EDDA-HYNICNF showed a higher abscess uptake and lower nontarget organ uptake and was able to distinguish bacterial infection and sterile inflammation. Single photon emission computed tomography (SPECT) image study in bacterial infection mice showed there was a visible accumulation in the infection site, suggesting that [Tc]Tc-EDDA-HYNICNF is a potential radiotracer for bacterial infection imaging.
为了寻找一种新型的用于细菌感染单光子发射计算机断层显像（SPECT）的锝标记喹诺酮衍生物，旨在降低非靶器官摄取，设计并合成了一种新型的诺氟沙星6-肼基烟酰胺（HYNIC）衍生物（HYNICNF）。用不同的共配体对其进行放射性标记，如三羟甲基氨基甲烷（tricine）、三苯基膦-3,3',3″-三磺酸钠（TPPTS）、三苯基膦-3-单磺酸钠（TPPMS）和乙二胺-N,N'-二乙酸（EDDA），以获得三种锝标记的诺氟沙星HYNIC配合物，即[Tc]Tc-tricine-TPPTS-HYNICNF、[Tc]Tc-tricine-TPPMS-HYNICNF和[Tc]Tc-EDDA-HYNICNF。对这些配合物进行了纯化（放射化学纯度>95%），并评估了它们对细菌的靶向性。所有三种配合物都具有亲水性，保持良好的稳定性，并且能特异性结合。细菌感染小鼠的生物分布研究表明，[Tc]Tc-EDDA-HYNICNF在脓肿部位摄取较高，在非靶器官摄取较低，并且能够区分细菌感染和无菌性炎症。细菌感染小鼠的单光子发射计算机断层显像（SPECT）图像研究显示，感染部位有明显的放射性积聚，这表明[Tc]Tc-EDDA-HYNICNF是一种用于细菌感染显像的潜在放射性示踪剂。
