Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Microbiology Unit, Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Biomolecules. 2021 Feb 5;11(2):232. doi: 10.3390/biom11020232.
Infectious diseases are one of the main causes of morbidity and mortality worldwide. Nuclear molecular imaging would be of great help to non-invasively discriminate between septic and sterile inflammation through available radiopharmaceuticals, as none is currently available for clinical practice. Here, we describe the radiolabeling procedure and in vitro and in vivo studies of Tc-polymyxin B sulfate (PMB) as a new single photon emission imaging agent for the characterization of infections due to Gram-negative bacteria.
Labeling efficiency was 97 ± 2% with an average molar activity of 29.5 ± 0.6 MBq/nmol. The product was highly stable in saline and serum up to 6 h. In vitro binding assay showed significant displaceable binding to Gram-negative bacteria but not to Gram-positive controls. In mice, Tc-HYNIC-PMB was mainly taken up by liver and kidneys. Targeting studies confirmed the specificity of Tc-HYNIC-PMB obtained in vitro, showing significantly higher T/B ratios for Gram-negative bacteria than Gram-positive controls.
In vitro and in vivo results suggest that Tc-HYNIC-PMB has a potential for in vivo identification of Gram-negative bacteria in patients with infections of unknown etiology. However, further investigations are needed to deeply understand the mechanism of action and behavior of Tc-HYNIC-PMB in other animal models and in humans.
传染病是全球发病率和死亡率的主要原因之一。通过现有的放射性药物，核分子成像将有助于非侵入性地区分脓毒症和无菌性炎症，因为目前尚无放射性药物可用于临床实践。在这里，我们描述了 Tc-多粘菌素 B 硫酸盐（PMB）作为一种新的单光子发射成像剂用于鉴定革兰氏阴性菌感染的放射性标记程序以及体外和体内研究。
标记效率为 97 ± 2%，平均摩尔活度为 29.5 ± 0.6 MBq/nmol。在生理盐水和血清中，产物在 6 小时内高度稳定。体外结合实验表明，与革兰氏阳性对照物相比，Tc-HYNIC-PMB 与革兰氏阴性细菌具有显著可置换的结合。在小鼠中，Tc-HYNIC-PMB 主要被肝脏和肾脏摄取。靶向研究证实了 Tc-HYNIC-PMB 在体外获得的特异性，显示出针对革兰氏阴性细菌的 T/B 比值明显高于革兰氏阳性对照物。
体外和体内结果表明，Tc-HYNIC-PMB 具有在感染病因不明的患者中体内识别革兰氏阴性细菌的潜力。然而，需要进一步研究以深入了解 Tc-HYNIC-PMB 在其他动物模型和人类中的作用机制和行为。
