In Vivo Optical Detection and Spectral Triangulation of Carbon Nanotubes

• Published in: ACS applied materials & interfaces Vol. 9; no. 48; pp. 41680 - 41690
• Main Authors: Lin, Ching-Wei, Yang, Hailing, Sanchez, Stephen R, Mao, Weiqun, Pang, Lan, Beckingham, Kathleen M, Bast, Robert C, Weisman, R. Bruce
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.12.2017
• Subjects: Animals; Fluorescence; Magnetic Resonance Imaging; Mice; Nanotubes, Carbon; Tomography, X-Ray Computed; short-wave infrared; mouse cancer models; in vivo fluorescence detection; ovarian cancer; single-walled carbon nanotubes; spectral triangulation; multimodal imaging
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.7b12916

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.