Early tumor detection afforded by in vivo imaging of near-infrared II fluorescence. (July 2017)

• Record Type: Journal Article
• Authors: Tao, Zhimin; Dang, Xiangnan; Huang, Xing; Muzumdar, Mandar D.; Xu, Eric S.; Bardhan, Neelkanth Manoj; Song, Haiqin; Qi, Ruogu; Yu, Yingjie; Li, Ting; Wei, Wei; Wyckoff, Jeffrey; Birrer, Michael J.; Belcher, Angela M.; Ghoroghchian, P. Peter
• Is Part Of: Biomaterials. Volume 134(2017)
• Page Start: 202
• Page End: 215
• Publication Date: 2017-07
• Subjects: Lanthanide nanoparticles -- Optical imaging -- Ovarian cancer -- Tumor targeting; DiR 1, 1'-dioctadecyl-3, 3, 3′, 3'-tetramethylindotricarbocyanine iodide -- DiR-Er, Tm/PEO-PCL DiR-encapsulated PEO5k-PCL16k-coated NaYF4:Yb, Er, Tm-based LNPs -- DiR-Er/PEO-PCL DiR-encapsulated PEO5k-PCL16k-coated NaYF4:Yb, Er-based LNPs -- DiR-Ho/Folate-PEO-PCL DiR-encapsulated, FA-conjugated, PEO6k-PCL16k-coated NaYF4:Yb, Ho-based LNPs -- DLS dynamic light scattering -- Er erbium -- InGaAs indium gallium arsenide -- IP intraperitoneal -- IV intravenous -- LNPs lanthanide nanoparticles -- LUC luciferase -- NIR near-infrared -- PDI polydispersity index -- PEO-b-PCL poly(ethylene oxide)-block-poly(ε-caprolactone) -- RFP red fluorescent protein -- NaYF4 sodium yttrium fluoride -- Tm thulium -- UC up-conversion -- Yb ytterbium -- Ho holmium; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2017.04.046
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Cell-intrinsic reporters such as luciferase (LUC) and red fluorescent protein (RFP) have been commonly utilized in preclinical studies to image tumor growth and to monitor therapeutic responses. While extrinsic reporters that emit near infrared I (NIR-I: 650–950 nm) or near-infrared II (NIR-II: 1000–1700 nm) optical signals have enabled minimization of tissue autofluorescence and light scattering, it has remained unclear as to whether their use has afforded more accurate tumor imaging in small animals. Here, we developed a novel optical imaging construct comprised of rare earth lanthanide nanoparticles coated with biodegradable diblock copolymers and doped with organic fluorophores, generating NIR-I and NIR-II emissive bands upon optical excitation. Simultaneous injection of multiple spectrally-unique nanoparticles into mice bearing tumor implants established via intraperitoneal dissemination of LUC + /RFP + OVCAR-8 ovarian cancer cells enabled direct comparisons of imaging with extrinsic vs. intrinsic reporters, NIR-II vs. NIR-I signals, as well as targeted vs. untargeted exogenous contrast agents in the same animal and over time. We discovered that in vivo optical imaging at NIR-II wavelengths facilitates more accurate detection of smaller and earlier tumor deposits, offering enhanced sensitivity, improved spatial contrast, and increased depths of tissue penetration as compared to imaging with visible or NIR-I fluorescent agents. Our work further highlights the hitherto underappreciated enhancements in tumor accumulation that may be achieved with intraperitoneal as opposed to intravenous administration of nanoparticles. Lastly, we found discrepancies in the fidelity of tumor uptake that could be obtained by utilizing small molecules for in vivo as opposed to in vitro targeting of nanoparticles to disseminated tumors.