title: Self-illuminating in vivo lymphatic imaging using a bioluminescence resonance energy transfer quantum dot nano-particle.
abstract: Autofluorescence arising from normal tissues can compromise the sensitivity and specificity of in vivo fluorescence imaging by lowering the target-to-background signal ratio. Since bioluminescence resonance energy transfer quantum dot (BRET-QDot) nano-particles can self-illuminate in near-infrared in the presence of the substrate, coelenterazine, without irradiating excitation lights, imaging using BRET-QDots does not produce any autofluorescence. In this study, we applied this BRET-QDot nano-particle to the in vivo lymphatic imaging in mice in order to compare with BRET, fluorescence or bioluminescence lymphatic imaging. BRET-QDot655, in which QDot655 is contained as a core, was injected at different sites (e.g. chin, ear, forepaws and hind paws) in mice followed by the intravenous coelenterazine injection, and then bioluminescence and fluorescence imaging were serially performed. In all mice, each lymphatic basin was clearly visualized in the BRET imaging with minimal background signals. The BRET signal in the lymph nodes lasted at least 30 min after coelenterazine injections. Furthermore, the BRET signal demonstrated better quantification than the fluorescence signal emitting from QDot655, the core of this BRET particle. These advantages of BRET-QDot allowed us to perform real-time, quantitative lymphatic imaging without image processing. BRET-Qdots have the potential to be a robust nano-material platform for developing optical molecular imaging probes.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1088, USA.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kosaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsunaga
authors.forename: Sukanta
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Steven C
authors.initials: SC
authors.lastname: Miller
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D008029:Lighting / Q000379:methods; D049408:Luminescent Agents / Q000737:chemistry; D008163:Luminescent Measurements / Q000379:methods*; D008208:Lymphatic System / Q000378:metabolism / Q000473:pathology; D008220:Lymphography / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D045663:Quantum Dots; D013997:Time Factors
chemical_list: D049408:Luminescent Agents