KleinJan Gijs Hendrik, Buckle Tessa, van Willigen Danny Michel, van Oosterom Matthias Nathanaël, Spa Silvia Johara, Kloosterboer Harmen Egbert, van Leeuwen Fijs Willem Bernhard
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.
Molecules. 2014 Jul 8;19(7):9876-92. doi: 10.3390/molecules19079876.
Damage to peripheral nerves caused during a surgical intervention often results in function loss. Fluorescence imaging has the potential to improve intraoperative identification and preservation of these structures. However, only very few nerve targeting agents are available. This study describes the in vivo nerve staining capabilities of locally administered fluorescent lectin-analogues. To this end WGA, PNA, PHA-L and LEL were functionalized with Cy5 (λex max 640 nm; λem max 680 nm). Transfer of these imaging agents along the sciatic nerve was evaluated in Thy1-YFP mice (n = 12) after intramuscular injection. Migration from the injection site was assessed in vivo using a laboratory fluorescence scanner and ex vivo via fluorescence confocal microscopy. All four lectins showed retrograde movement and staining of the epineurium with a signal-to-muscle ratio of around two. On average, the longest transfer distance was obtained with WGA-Cy5 (0.95 cm). Since WGA also gave minimal uptake in the lymphatic system, this lectin type revealed the highest potential as a migration imaging agent to visualize nerves.
手术干预过程中造成的周围神经损伤常常导致功能丧失。荧光成像有潜力改善术中对这些结构的识别和保护。然而,可用的神经靶向剂非常少。本研究描述了局部施用的荧光凝集素类似物在体内的神经染色能力。为此,用Cy5(激发波长最大值640nm;发射波长最大值680nm)对小麦胚凝集素(WGA)、花生凝集素(PNA)、菜豆凝集素(PHA-L)和荆豆凝集素(LEL)进行功能化修饰。在肌肉注射后,于Thy1-YFP小鼠(n = 12)中评估这些成像剂沿坐骨神经的转移情况。使用实验室荧光扫描仪在体内评估从注射部位的迁移,并通过荧光共聚焦显微镜在体外进行评估。所有四种凝集素均显示逆行移动和神经外膜染色,信号与肌肉的比率约为2。平均而言,WGA-Cy5的转移距离最长(0.95厘米)。由于WGA在淋巴系统中的摄取也最少,这种凝集素作为用于可视化神经的迁移成像剂显示出最高的潜力。