Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Nucl Med Biol. 2010 Jan;37(1):29-34. doi: 10.1016/j.nucmedbio.2009.08.011. Epub 2009 Oct 3.
Abscess formation causes systemic and localized up-regulation of neutrophil [polymorphonuclear leukocytes (PMNs)] signaling pathways. In the abscess, following bacterial ingestion or PMN activation by inflammatory mediators, PMN apoptosis is elevated and leads to the externalization of phosphatidylserine. Annexin-V (AnxV) has been shown to have high affinity to externalized phosphatidylserine. We hypothesized that (99m)Tc-AnxV will target high densities of apoptotic PMNs and image abscesses. AnxV, conjugated with hydrazinenicaotinamide (HYNIC), was labeled with reduced (99m)TcO(4)(-) and its purity was determined by instant thin-layer chromatography. Apoptosis was induced in isolated human PMNs by incubation in 2% saline for 17 and 22 h at 37 degrees C. PMNs were then incubated with (99m)Tc-HYNIC-AnxV and associated (99m)Tc was determined. Abscesses were induced in mice by intramuscular injection of bacteria or turpentine. Following intravenous administration of (99m)Tc-HYNIC-AnxV, mice were imaged and tissue distribution studied at 4 and 24 h. Radiochemical purity of (99m)Tc-HYNIC-AnxV was 84.9+/-8.11%. At 17 h, (99m)Tc-HYNIC-AnxV bound to apoptotic PMNs was 71.6+/-0.01% and 48.6+/-0.01% for experimental and control cells, respectively (P=.002). At 22 h, experimental cells retained 74.9+/-0.02% and control cells retained 47.2+/-0.02% (P=.005). (99m)Tc-HYNIC-AnxV associated with bacterial abscesses was 1.25+/-0.09 and 3.75+/-0.83 percent injected dose per gram (%ID/g) at 4 and 24 h compared to turpentine abscesses which was 1.02+/-0.16 and 0.72+/-0.17 %ID/g at 4 (P<or=.05) and 24 h (P<or=.01). (99m)Tc-HYNIC-AnxV represents a minimally invasive and promising agent to image and potentially distinguish between infectious and inflammatory abscesses.
脓肿形成会导致中性粒细胞（多形核白细胞）的系统和局部信号通路上调。在脓肿中，细菌摄取或炎症介质激活中性粒细胞后，中性粒细胞凋亡增加，导致磷脂酰丝氨酸外化。已经证明， annexin-V（AnxV）与外化的磷脂酰丝氨酸具有高亲和力。我们假设（99m）Tc-AnxV 将靶向高浓度凋亡的中性粒细胞并对脓肿进行成像。AnxV 与肼基烟酰胺（HYNIC）缀合，并用还原的（99m）TcO（4）（-）标记，并通过即时薄层层析法确定其纯度。分离的人中性粒细胞在 2%盐水孵育 17 和 22 小时，在 37°C 下孵育。然后将中性粒细胞与（99m）Tc-HYNIC-AnxV 孵育，并测定相关的（99m）Tc。通过肌肉内注射细菌或松节油在小鼠中诱导脓肿。静脉内给予（99m）Tc-HYNIC-AnxV 后，在 4 和 24 小时进行小鼠成像并研究组织分布。（99m）Tc-HYNIC-AnxV 的放射化学纯度为 84.9+/-8.11%。在 17 小时时，（99m）Tc-HYNIC-AnxV 与凋亡的中性粒细胞结合的比例分别为实验细胞 71.6+/-0.01%和对照细胞 48.6+/-0.01%（P=.002）。在 22 小时时，实验细胞保留 74.9+/-0.02%，对照细胞保留 47.2+/-0.02%（P=.005）。与松节油脓肿相比，与细菌脓肿相关的（99m）Tc-HYNIC-AnxV 在 4 和 24 小时时分别为 1.25+/-0.09 和 3.75+/-0.83 每克注射剂量%（%ID/g）（P<0.05）和 24 小时（P<0.01）。（99m）Tc-HYNIC-AnxV 是一种微创且有前途的成像剂，可用于成像，并有可能区分感染性和炎症性脓肿。
