Utilizing the power of Cerenkov light with nanotechnology.

The characteristic blue glow of Cerenkov luminescence (CL) arises from the interaction between a charged particle travelling faster than the phase velocity of light and a dielectric medium, such as water or tissue. As CL emanates from a variety of sources, such as cosmic events, particle accelerators, nuclear reactors and clinical radionuclides, it has been used in applications such as particle detection, dosimetry, and medical imaging and therapy. The combination of CL and nanoparticles for biomedicine has improved diagnosis and therapy, especially in oncological research. Although radioactive decay itself cannot be easily modulated, the associated CL can be through the use of nanoparticles, thus offering new applications in biomedical research. Advances in nanoparticles, metamaterials and photonic crystals have also yielded new behaviours of CL. Here, we review the physics behind Cerenkov luminescence and associated applications in biomedicine. We also show that by combining advances in nanotechnology and materials science with CL, new avenues for basic and applied sciences have opened.

[1]  Molecular imaging using nanoparticle quenchers of Cerenkov luminescence. , 2014, Small.

[2]  W. Kreyling,et al.  Radiolabelling of engineered nanoparticles for in vitro and in vivo tracing applications using cyclotron accelerators , 2011, Archives of Toxicology.

[3]  Hans Tanke,et al.  Optical imaging as an expansion of nuclear medicine: Cerenkov-based luminescence vs fluorescence-based luminescence , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[4]  Yichen Shen,et al.  Efficient plasmonic emission by the quantum Čerenkov effect from hot carriers in graphene , 2016, Nature Communications.

[5]  V. Baryshevsky,et al.  Cooperative parametric (quasi-Cherenkov) radiation produced by electron bunches in natural or photonic crystals , 2015 .

[6]  Zhen Cheng,et al.  Radiation-luminescence-excited quantum dots for in vivo multiplexed optical imaging. , 2010, Small.

[7]  A P Gibson,et al.  The physics of Cerenkov light production during proton therapy , 2014, Physics in medicine and biology.

[8]  K. Tsakmakidis,et al.  ‘Trapped rainbow’ storage of light in metamaterials , 2007, Nature.

[9]  Jan Danckaert,et al.  Controlling Cherenkov radiation with transformation-optical metamaterials. , 2014, Physical review letters.

[10]  Jiangtao Huangfu,et al.  A Viewpoint on: Experimental Verification of Reversed Cherenkov Radiation in Left-Handed Metamaterial , 2009 .

[11]  S. Wu,et al.  Experimental Observation of a Heavy Particle $J$ , 1974 .

[12]  Jeffrey James,et al.  An emerging paradigm , 2004 .

[13]  John Power,et al.  Observation of Wakefield Generation in Left-Handed Band of Metamaterial-Loaded Waveguide , 2008 .

[14]  Jan Grimm,et al.  Quantitative imaging of disease signatures through radioactive decay signal conversion , 2013, Nature Medicine.

[15]  Natalia G. Zhegalova,et al.  In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging. , 2016, Biomaterials.

[16]  P. A. Čerenkov Visible radiation produced by electrons moving in a medium with velocities exceeding that of light , 1937 .

[17]  Rcip-Chin The Emission Spectrum , 2011 .

[18]  Stewart,et al.  Extremely low frequency plasmons in metallic mesostructures. , 1996, Physical review letters.

[19]  Wei Fan,et al.  Dye-Sensitized Core/Active Shell Upconversion Nanoparticles for Optogenetics and Bioimaging Applications. , 2016, ACS nano.

[20]  John L. Humm,et al.  Quantitative Modeling of Cerenkov Light Production Efficiency from Medical Radionuclides , 2012, PloS one.

[21]  Jin Chang,et al.  Intrinsically Radioactive [64Cu]CuInS/ZnS Quantum Dots for PET and Optical Imaging: Improved Radiochemical Stability and Controllable Cerenkov Luminescence , 2014, ACS nano.

[22]  Johan Axelsson,et al.  (68)Ga-labeled superparamagnetic iron oxide nanoparticles (SPIONs) for multi-modality PET/MR/Cherenkov luminescence imaging of sentinel lymph nodes. , 2013, American journal of nuclear medicine and molecular imaging.

[23]  Christopher B. Murray,et al.  Shape-Controlled Synthesis of Isotopic Yttrium-90-Labeled Rare Earth Fluoride Nanocrystals for Multimodal Imaging. , 2015, ACS nano.

[24]  Jan Grimm,et al.  Clinical Cerenkov Luminescence Imaging of 18F-FDG , 2014, The Journal of Nuclear Medicine.

[25]  Z. Jacob,et al.  Quantum nanophotonics using hyperbolic metamaterials , 2012, 1204.5529.

[26]  Peng Huang,et al.  PET and NIR optical imaging using self-illuminating (64)Cu-doped chelator-free gold nanoclusters. , 2014, Biomaterials.

[27]  Zhe Wang,et al.  Enhancement of Cerenkov Luminescence Imaging by Dual Excitation of Er3+, Yb3+-Doped Rare-Earth Microparticles , 2013, PloS one.

[28]  William H. Lee,et al.  Sensitivity of the high altitude water Cherenkov detector to sources of multi-TeV gamma rays , 2013, 1306.5800.

[29]  A. Kobzev On the radiation mechanism of a uniformly moving charge , 2014, Physics of Particles and Nuclei.

[30]  Carlo Cavedon,et al.  First human Cerenkography , 2013, Journal of biomedical optics.

[31]  Jie Zheng,et al.  Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics. , 2012, Angewandte Chemie.

[32]  T. Reiner,et al.  Cerenkov Luminescence Imaging for Radiation Dose Calculation of a 90Y-Labeled Gastrin-Releasing Peptide Receptor Antagonist , 2015, The Journal of Nuclear Medicine.

[33]  E. Yablonovitch,et al.  Inhibited spontaneous emission in solid-state physics and electronics. , 1987, Physical review letters.

[34]  Hongsheng Chen,et al.  Flipping photons backward: reversed Cherenkov radiation , 2011 .

[35]  G. E. Fischer,et al.  Discovery of a Narrow Resonance in $e^+ e^-$ Annihilation , 1974 .

[36]  M. Wegener,et al.  Negative Refractive Index at Optical Wavelengths , 2007, Science.

[37]  Steven G. Johnson,et al.  Cerenkov Radiation in Photonic Crystals , 2003, Science.

[38]  O. Chamberlain,et al.  OBSERVATION OF ANTIPROTONS , 1955 .

[39]  Byeong-Cheol Ahn,et al.  Combined Positron Emission Tomography and Cerenkov Luminescence Imaging of Sentinel Lymph Nodes Using PEGylated Radionuclide-Embedded Gold Nanoparticles. , 2016, Small.

[40]  Sung-Joo Hwang,et al.  Liposomal drug products and recent advances in the synthesis of supercritical fluid-mediated liposomes. , 2013, Nanomedicine.

[41]  Xin Cai,et al.  Radioactive 198Au-Doped Nanostructures with Different Shapes for In Vivo Analyses of Their Biodistribution, Tumor Uptake, and Intratumoral Distribution , 2014, ACS nano.

[42]  D. Chigrin,et al.  Theory of Cherenkov radiation in periodic dielectric media: Emission spectrum , 2008, 0808.3519.

[43]  Qi Jie Wang,et al.  Reverse surface-polariton cherenkov radiation , 2016, Scientific Reports.

[44]  Scott C Davis,et al.  Three-dimensional Čerenkov tomography of energy deposition from ionizing radiation beams. , 2013, Optics letters.

[45]  V. Shalaev Optical negative-index metamaterials , 2007 .

[46]  Anna Moore,et al.  In Vivo Photoactivation Without “Light”: Use of Cherenkov Radiation to Overcome the Penetration Limit of Light , 2011, Molecular Imaging and Biology.

[47]  King Li,et al.  Preliminary Therapy Evaluation of 225Ac-DOTA-c(RGDyK) Demonstrates that Cerenkov Radiation Derived from 225Ac Daughter Decay Can Be Detected by Optical Imaging for In Vivo Tumor Visualization , 2016, Theranostics.

[48]  Yong Ding,et al.  Self-Illuminating 64Cu-Doped CdSe/ZnS Nanocrystals for in Vivo Tumor Imaging , 2014, Journal of the American Chemical Society.

[49]  Chulhong Kim,et al.  Hexamodal Imaging with Porphyrin‐Phospholipid‐Coated Upconversion Nanoparticles , 2015, Advanced materials.

[50]  Byeong-Cheol Ahn,et al.  Radionuclide-embedded gold nanoparticles for enhanced dendritic cell-based cancer immunotherapy, sensitive and quantitative tracking of dendritic cells with PET and Cerenkov luminescence , 2016 .

[51]  H. Lezec,et al.  Negative Refraction at Visible Frequencies , 2007, Science.

[52]  S. Skirlo,et al.  Quantum Čerenkov Radiation: Spectral Cutoffs and the Role of Spin and Orbital Angular Momentum , 2014, 1411.0083.

[53]  Riccardo Calandrino,et al.  In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[54]  Feng Chen,et al.  In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles , 2015, ACS nano.

[55]  Zhen Cheng,et al.  Endoscopic imaging of Cerenkov luminescence , 2012, Biomedical optics express.

[56]  Daniel Wintz,et al.  Controlled steering of Cherenkov surface plasmon wakes with a one-dimensional metamaterial , 2015, 2015 Conference on Lasers and Electro-Optics (CLEO).

[57]  B. Pogue,et al.  Cherenkov radiation fluence estimates in tissue for molecular imaging and therapy applications. , 2015, Physics in medicine and biology.

[58]  J. Pendry,et al.  Negative refraction makes a perfect lens , 2000, Physical review letters.

[59]  A. Kobzev The mechanism of Vavilov-Cherenkov radiation , 2010 .

[60]  J. Kong,et al.  Cerenkov radiation in materials with negative permittivity and permeability. , 2003, Optics express.

[61]  Weibo Cai,et al.  Cerenkov Radiation Induced Photodynamic Therapy Using Chlorin e6-Loaded Hollow Mesoporous Silica Nanoparticles. , 2016, ACS applied materials & interfaces.

[62]  Feng Chen,et al.  Intrinsically radiolabeled nanoparticles: an emerging paradigm. , 2014, Small.

[63]  Jan Grimm,et al.  Cerenkov imaging - a new modality for molecular imaging. , 2012, American journal of nuclear medicine and molecular imaging.

[64]  Yei Hwan Jung,et al.  Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics , 2013, Science.

[65]  David R. Smith,et al.  A full-parameter unidirectional metamaterial cloak for microwaves. , 2013, Nature materials.

[66]  Jan Grimm,et al.  Intraoperative Imaging of Positron Emission Tomographic Radiotracers Using Cerenkov Luminescence Emissions , 2011, Molecular imaging.

[67]  R. Merlin,et al.  Cherenkov radiation at speeds below the light threshold: phonon-assisted phase matching. , 2001, Science.

[68]  Jan Grimm,et al.  Positron Lymphography: Multimodal, High-Resolution, Dynamic Mapping and Resection of Lymph Nodes After Intradermal Injection of 18F-FDG , 2012, The Journal of Nuclear Medicine.

[69]  Jan Grimm,et al.  Stable Radiolabeling of Sulfur-Functionalized Silica Nanoparticles with Copper-64. , 2016, Nano letters.

[70]  Samuel Achilefu,et al.  Activatable probes based on distance-dependent luminescence associated with Cerenkov radiation. , 2013, Angewandte Chemie.

[71]  Valerie A Longo,et al.  A Modular Labeling Strategy for In Vivo PET and Near-Infrared Fluorescence Imaging of Nanoparticle Tumor Targeting , 2014, The Journal of Nuclear Medicine.

[72]  Jan Grimm,et al.  Silica Nanoparticles as Substrates for Chelator-free Labeling of Oxophilic Radioisotopes , 2015, Nano letters.

[73]  Jie Tian,et al.  In vivo nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging , 2015, Nature Communications.

[74]  I. Tamm,et al.  Coherent visible radiation of fast electrons passing through matter , 1937 .

[75]  Samuel Achilefu,et al.  Breaking the Depth Dependency of Phototherapy with Cerenkov Radiation and Low Radiance Responsive Nanophotosensitizers , 2015, Nature nanotechnology.

[76]  S R Cherry,et al.  Optical imaging of Cerenkov light generation from positron-emitting radiotracers , 2009, Physics in medicine and biology.

[77]  Mário G. Silveirinha,et al.  Cherenkov emission in a nanowire material , 2012 .

[78]  G. Park,et al.  Surface-coupling of Cerenkov radiation from a modified metallic metamaterial slab via Brillouin-band folding. , 2014, Optics express.

[79]  Erin Jackson,et al.  Cerenkov Radiation Energy Transfer (CRET) Imaging: A Novel Method for Optical Imaging of PET Isotopes in Biological Systems , 2010, PloS one.

[80]  Bo Liu,et al.  Nanoparticle-aided external beam radiotherapy leveraging the Čerenkov effect. , 2016, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[81]  Brian W. Pogue,et al.  Projection imaging of photon beams by the Čerenkov effect. , 2012, Medical physics.

[82]  Alice M. Bowen,et al.  Chelate-free metal ion binding and heat-induced radiolabeling of iron oxide nanoparticles† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc02778g Click here for additional data file. , 2014, Chemical science.

[83]  Yongmin Chang,et al.  Vivid tumor imaging utilizing liposome-carried bimodal radiotracer. , 2014, ACS medicinal chemistry letters.

[84]  Andrea R Tao,et al.  Colloidal metasurfaces displaying near-ideal and tunable light absorbance in the infrared , 2015, Nature Communications.

[85]  Gun-Sik Park,et al.  Cerenkov radiation in metallic metamaterials , 2010 .

[86]  Boris M. Bolotovskii Vavilov – Cherenkov radiation: its discovery and application , 2009 .

[87]  V. Veselago The Electrodynamics of Substances with Simultaneously Negative Values of ∊ and μ , 1968 .

[88]  Joanne Li,et al.  Enhancement and wavelength-shifted emission of Cerenkov luminescence using multifunctional microspheres , 2015, Physics in medicine and biology.

[89]  S. Cherry,et al.  Computed Cerenkov luminescence yields for radionuclides used in biology and medicine , 2015, Physics in medicine and biology.

[90]  Jan-Olov Liljenzin,et al.  Radiochemistry And Nuclear Chemistry , 1995 .

[91]  Willie J Padilla,et al.  Composite medium with simultaneously negative permeability and permittivity , 2000, Physical review letters.

[92]  Karen L Wooley,et al.  Copper-64-alloyed gold nanoparticles for cancer imaging: improved radiolabel stability and diagnostic accuracy. , 2014, Angewandte Chemie.

[93]  M. Wegener,et al.  Past achievements and future challenges in the development of three-dimensional photonic metamaterials , 2011 .