Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, 318 Campus Drive, Stanford, CA 94305, USA.
Small. 2011 Aug 8;7(15):2232-40. doi: 10.1002/smll.201002317. Epub 2011 May 24.
Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endoscopy. The use of an accessory Raman endoscope in conjunction with topically administered tumor-targeting Raman nanoparticles during a routine colonoscopy could offer a new way to sensitively detect dysplastic lesions while circumventing Raman's limited depth of penetration and avoiding systemic toxicity. In this study, the natural biodistribution of gold surface-enhanced Raman scattering (SERS) nanoparticles is evaluated by radiolabeling them with (64) Cu and imaging their localization over time using micropositron emission tomography (PET). Mice are injected either intravenously (IV) or intrarectally (IR) with approximately 100 microcuries (μCi) (3.7 megabecquerel (MBq)) of (64) Cu-SERS nanoparticles and imaged with microPET at various time points post injection. Quantitative biodistribution data are obtained as % injected dose per gram (%ID g(-1)) from each organ, and the results correlate well with the corresponding microPET images, revealing that IV-injected mice have significantly higher uptake (p < 0.05) in the liver (5 h = 8.96% ID g(-1); 24 h = 8.27% ID g(-1)) than IR-injected mice (5 h = 0.09% ID g(-1); 24 h = 0.08% ID g(-1)). IR-injected mice show localized uptake in the large intestine (5 h = 10.37% ID g(-1); 24 h = 0.42% ID g(-1)) with minimal uptake in other organs. Raman imaging of excised tissues correlate well with biodistribution data. These results suggest that the topical application of SERS nanoparticles in the mouse colon appears to minimize their systemic distribution, thus avoiding potential toxicity and supporting the clinical translation of Raman spectroscopy as an endoscopic imaging tool.
拉曼成像是一种具有无与伦比的灵敏度和多路复用能力的技术。然而，其有限的光穿透深度使得其在临床中的直接转化具有挑战性。因此，在临床环境中利用其属性的更合适方法是将拉曼光谱与内窥镜相结合。在常规结肠镜检查中，使用附件式拉曼内窥镜结合局部施用的肿瘤靶向拉曼纳米颗粒，可能为敏感地检测发育不良病变提供一种新方法，同时避免拉曼有限的穿透深度并避免全身毒性。在这项研究中，通过用 (64)Cu 标记金表面增强拉曼散射 (SERS) 纳米颗粒并使用微正电子发射断层扫描 (microPET) 随时间对其定位来评估它们的自然生物分布。将约 100 微居里 (μCi) (3.7 兆贝克勒尔 (MBq)) 的 (64)Cu-SERS 纳米颗粒通过静脉内 (IV) 或直肠内 (IR) 注射到小鼠体内，并在注射后不同时间点使用 microPET 进行成像。从每个器官获得的定量生物分布数据为每克注入剂量的百分比 (%ID g(-1))，结果与相应的 microPET 图像很好地相关，表明 IV 注射的小鼠肝脏摄取率显著更高 (p < 0.05)(5 h = 8.96% ID g(-1); 24 h = 8.27% ID g(-1))比 IR 注射的小鼠 (5 h = 0.09% ID g(-1); 24 h = 0.08% ID g(-1))。IR 注射的小鼠在大肠中显示局部摄取 (5 h = 10.37% ID g(-1); 24 h = 0.42% ID g(-1))，而其他器官摄取量最小。对切除组织的拉曼成像与生物分布数据很好地相关。这些结果表明，SERS 纳米颗粒在小鼠结肠中的局部应用似乎最大限度地减少了它们的全身分布，从而避免了潜在的毒性，并支持了拉曼光谱作为内窥镜成像工具的临床转化。
