Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center , Houston, Texas 77030, United States.
ACS Appl Mater Interfaces. 2017 Dec 6;9(48):41680-41690. doi: 10.1021/acsami.7b12916. Epub 2017 Nov 27.
In the first in vivo demonstration of spectral triangulation, biocompatible composites of single-walled carbon nanotubes in Matrigel have been surgically implanted into mouse ovaries and then noninvasively detected and located. This optical method deduces the three-dimensional position of a short-wave IR emission source from the wavelength-dependent attenuation of fluorescence in tissues. Measurements were performed with a second-generation optical scanner that uses a light-emitting diode matrix emitting at 736 nm for diffuse specimen excitation. The intrinsic short-wave IR fluorescence of the nanotubes was collected at various positions on the specimen surface, spectrally filtered, and detected by a photon-counting InGaAs avalanche photodiode. Sensitivity studies showed a detection limit of ∼120 pg of nanotubes located beneath ∼3 mm of tissue. In addition, the mass and location of implanted nanotubes could be deduced through spectral triangulation with sub-millimeter accuracy, as validated with the aid of magnetic resonance imaging (MRI) data. Dual-modality imaging combining spectral triangulation with computed tomography or MRI will allow accurate registration of emission centers with anatomical features. These results are a step toward the future use of probes with targeting agents such as antibodies linked to nanotube tags for the noninvasive detection and imaging of tumors in preclinical research on small animals. Translation to the clinic could aid in early detection of ovarian cancer and identification of metastases for resection during primary surgery.
在光谱三角测量的首次体内演示中,将单壁碳纳米管的生物相容性复合材料通过手术植入到小鼠卵巢中,然后进行非侵入式检测和定位。这种光学方法通过组织中荧光的波长相关衰减来推断短波长红外发射源的三维位置。使用第二代光学扫描仪进行了测量,该扫描仪使用发出 736nm 光的发光二极管矩阵对漫射样本进行激发。在样品表面的不同位置收集纳米管的固有短波长红外荧光,进行光谱滤波,并通过光子计数型 InGaAs 雪崩光电二极管进行检测。灵敏度研究表明,在大约 3mm 的组织下方可以检测到约 120pg 的纳米管,检测限约为 120pg。此外,通过光谱三角测量可以精确推断出植入纳米管的质量和位置,其准确性可通过磁共振成像 (MRI) 数据进行验证。将光谱三角测量与计算机断层扫描或 MRI 相结合的双模成像,将允许发射中心与解剖特征进行精确配准。这些结果是朝着未来使用带有靶向剂(如与纳米管标签相连的抗体)的探针的方向迈进的一步,可用于小动物临床前研究中对肿瘤进行非侵入式检测和成像。该技术应用于临床有助于早期发现卵巢癌并识别原发性手术中的转移灶。