The evolution of gadolinium based contrast agents: from single-modality to multi-modality.

Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications.

[1]  Marco Giardiello,et al.  Cell-permeable Ln(III) chelate-functionalized InP quantum dots as multimodal imaging agents. , 2011, ACS nano.

[2]  Dapeng Liu,et al.  ZnO-functionalized upconverting nanotheranostic agent: multi-modality imaging-guided chemotherapy with on-demand drug release triggered by pH. , 2014, Angewandte Chemie.

[3]  R. Price,et al.  First soluble M@C60 derivatives provide enhanced access to metallofullerenes and permit in vivo evaluation of Gd@C60[C(COOH)2]10 as a MRI contrast agent. , 2003, Journal of the American Chemical Society.

[4]  Wei Zhang,et al.  The synthesis of a D-glucosamine contrast agent, Gd-DTPA-DG, and its application in cancer molecular imaging with MRI. , 2011, European journal of radiology.

[5]  K. Nicolay,et al.  Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis , 2010, Angiogenesis.

[6]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[7]  Yun Sun,et al.  Fluorine-18-labeled Gd3+/Yb3+/Er3+ co-doped NaYF4 nanophosphors for multimodality PET/MR/UCL imaging. , 2011, Biomaterials.

[8]  Y. Bae,et al.  A cancer-recognizable MRI contrast agents using pH-responsive polymeric micelle. , 2014, Biomaterials.

[9]  Teri W. Odom,et al.  High relaxivity Gd(III)-DNA gold nanostars: investigation of shape effects on proton relaxation. , 2015, ACS nano.

[10]  M. Griswold,et al.  Peptide targeted tripod macrocyclic Gd(III) chelates for cancer molecular MRI. , 2013, Biomaterials.

[11]  K. Nicolay,et al.  Influence of cell-internalization on relaxometric, optical and compositional properties of targeted paramagnetic quantum dot micelles. , 2011, Contrast media & molecular imaging.

[12]  Zhen Wei,et al.  Poly(vinyl alcohol) electrospun nanofibrous membrane modified with spirolactam–rhodamine derivatives for visible detection and removal of metal ions , 2014 .

[13]  Xiao Zhang,et al.  Recent Advances in Upconversion Nanoparticles‐Based Multifunctional Nanocomposites for Combined Cancer Therapy , 2015, Advanced materials.

[14]  Soojin Lim,et al.  NIR dyes for bioimaging applications. , 2010, Current opinion in chemical biology.

[15]  Jun‐Jie Zhu,et al.  Reversible switches of DNA nanostructures between "Closed" and "Open" states and their biosensing applications. , 2013, Nanoscale.

[16]  Joop A. Peters,et al.  Prototropic Exchange Governs T-1 and T-2 Relaxivities of a Potential MRI Contrast Agent Nanozeolite Gd-LTL with a High pH Responsiveness , 2015 .

[17]  D. Parker,et al.  Noninvasive Visualization of Pharmacokinetics, Biodistribution and Tumor Targeting of Poly[N-(2-hydroxypropyl)methacrylamide] in Mice Using Contrast Enhanced MRI , 2007, Pharmaceutical Research.

[18]  Rex Moats,et al.  Integrin α2β1 targeted GdVO4:Eu ultrathin nanosheet for multimodal PET/MR imaging. , 2014, Biomaterials.

[19]  Guoying Zhang,et al.  Synergistically enhance magnetic resonance/fluorescence imaging performance of responsive polymeric nanoparticles under mildly acidic biological milieu. , 2013, Macromolecular rapid communications.

[20]  C. Brennan,et al.  A Brain Tumor Molecular Imaging Strategy Using A New Triple-Modality MRI-Photoacoustic-Raman Nanoparticle , 2011, Nature Medicine.

[21]  Z. Lu,et al.  HPMA copolymer-anticancer drug conjugates: design, activity, and mechanism of action. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[22]  Angelique Y. Louie,et al.  Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging. , 2007 .

[23]  E. Jeong,et al.  Noninvasive visualization of in vivo drug delivery of poly(L-glutamic acid) using contrast-enhanced MRI. , 2006, Molecular pharmaceutics.

[24]  R. Pei,et al.  Aptamer-Modified Temperature-Sensitive Liposomal Contrast Agent for Magnetic Resonance Imaging. , 2015, Biomacromolecules.

[25]  P. Chu,et al.  Smart polymeric particle encapsulated gadolinium oxide and europium: theranostic probes for magnetic resonance/optical imaging and antitumor drug delivery. , 2016, Journal of materials chemistry. B.

[26]  Y. Ling,et al.  Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery. , 2015, Journal of materials chemistry. B.

[27]  Baris Turkbey,et al.  Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[28]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[29]  Jingliang Cheng,et al.  Facile synthesis of gadolinium (III) chelates functionalized carbon quantum dots for fluorescence and magnetic resonance dual-modal bioimaging , 2015 .

[30]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[31]  H. Kong,et al.  A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging. , 2013, ACS nano.

[32]  S. Nair,et al.  Multifunctional calcium phosphate nano-contrast agent for combined nuclear, magnetic and near-infrared in vivo imaging. , 2013, Biomaterials.

[33]  P. Fries,et al.  Confinement of a tris-aqua Gd(iii) complex in silica nanoparticles leads to high stability and high relaxivity and supresses anion binding. , 2015, Chemical communications.

[34]  Xianglong Hu,et al.  Cell-penetrating hyperbranched polyprodrug amphiphiles for synergistic reductive milieu-triggered drug release and enhanced magnetic resonance signals. , 2015, Journal of the American Chemical Society.

[35]  Jun Lin,et al.  In vivo multimodality imaging and cancer therapy by near-infrared light-triggered trans-platinum pro-drug-conjugated upconverison nanoparticles. , 2013, Journal of the American Chemical Society.

[36]  E. Scott,et al.  Gadolinium-doped silica nanoparticles encapsulating indocyanine green for near infrared and magnetic resonance imaging. , 2012, Small.

[37]  E. Que,et al.  Responsive magnetic resonance imaging contrast agents as chemical sensors for metals in biology and medicine. , 2010, Chemical Society reviews.

[38]  Xing Wu,et al.  MR imaging of tumor angiogenesis using sterically stabilized Gd-DTPA liposomes targeted to CD105. , 2009, European journal of radiology.

[39]  Ande Bao,et al.  Novel multifunctional theranostic liposome drug delivery system: construction, characterization, and multimodality MR, near-infrared fluorescent, and nuclear imaging. , 2012, Bioconjugate chemistry.

[40]  Lehui Lu,et al.  Fluorescence-enhanced gadolinium-doped zinc oxide quantum dots for magnetic resonance and fluorescence imaging. , 2011, Biomaterials.

[41]  T. Krasia‐Christoforou,et al.  Polymeric theranostics: using polymer-based systems for simultaneous imaging and therapy. , 2013, Journal of materials chemistry. B.

[42]  S. Feng,et al.  Aqueous phase synthesis of upconversion nanocrystals through layer-by-layer epitaxial growth for in vivo X-ray computed tomography. , 2013, Nanoscale.

[43]  Kouichi Shiraishi,et al.  Preparation and in vivo imaging of PEG-poly(L-lysine)-based polymeric micelle MRI contrast agents. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[44]  Ming Wu,et al.  Lipid micelles packaged with semiconducting polymer dots as simultaneous MRI/photoacoustic imaging and photodynamic/photothermal dual-modal therapeutic agents for liver cancer. , 2016, Journal of materials chemistry. B.

[45]  Duyang Gao,et al.  Hybrid gold-gadolinium nanoclusters for tumor-targeted NIRF/CT/MRI triple-modal imaging in vivo. , 2013, Nanoscale.

[46]  Hyun-Jong Cho,et al.  Self-assembled magnetic resonance imaging nanoprobes based on arachidyl chitosan for cancer diagnosis. , 2013, Colloids and surfaces. B, Biointerfaces.

[47]  Nuria Genicio,et al.  Sugar/gadolinium-loaded gold nanoparticles for labelling and imaging cells by magnetic resonance imaging. , 2013, Biomaterials science.

[48]  Andrew V. Sutherland,et al.  Molecular tracers for the PET and SPECT imaging of disease. , 2011, Chemical Society reviews.

[49]  T. Hyeon,et al.  Nanostructured T1 MRI contrast agents , 2009 .

[50]  P. Chandrasekharan,et al.  Gadolinium chelate with DO3A conjugated 2-(diphenylphosphoryl)-ethyldiphenylphosphonium cation as potential tumor-selective MRI contrast agent. , 2012, Biomaterials.

[51]  Dongmei Yang,et al.  Fabrication of hollow and porous structured GdVO4:Dy3+ nanospheres as anticancer drug carrier and MRI contrast agent. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[52]  P ? ? ? ? ? ? ? % ? ? ? ? , 1991 .

[53]  A. S. Moses,et al.  Imaging and drug delivery using theranostic nanoparticles. , 2010, Advanced drug delivery reviews.

[54]  Qi Zhang,et al.  Evaluation of diethylenetriaminepentaacetic acid-manganese(II) complexes modified by narrow molecular weight distribution of chitosan oligosaccharides as potential magnetic resonance imaging contrast agents. , 2011, Magnetic resonance imaging.

[55]  Lin Yu,et al.  Influence of LA and GA sequence in the PLGA block on the properties of thermogelling PLGA-PEG-PLGA block copolymers. , 2011, Biomacromolecules.

[56]  R. Weissleder,et al.  Molecular imaging in drug discovery and development , 2003, Nature Reviews Drug Discovery.

[57]  Kristen M. Jaruszewski,et al.  Multimodal nanoprobes to target cerebrovascular amyloid in Alzheimer's disease brain. , 2014, Biomaterials.

[58]  Gang Liu,et al.  A Synergistically Enhanced T1–T2 Dual‐Modal Contrast Agent , 2012, Advanced materials.

[59]  M. Brechbiel,et al.  Preparation, characterization and in vivo assessment of Gd-albumin and Gd-dendrimer conjugates as intravascular contrast-enhancing agents for MRI. , 2011, Journal of inorganic biochemistry.

[60]  Erlong Zhang,et al.  A review of NIR dyes in cancer targeting and imaging. , 2011, Biomaterials.

[61]  Piper J. Klemm,et al.  Analysis of Lanthanide Complex Dendrimer Conjugates for Bimodal NIR and MRI Imaging. , 2012, Macromolecules.

[62]  Qingfeng Xiao,et al.  Rattle-structured multifunctional nanotheranostics for synergetic chemo-/radiotherapy and simultaneous magnetic/luminescent dual-mode imaging. , 2013, Journal of the American Chemical Society.

[63]  R. Nitschke,et al.  Quantum dots versus organic dyes as fluorescent labels , 2008, Nature Methods.

[64]  M. Delville,et al.  Lanthanide-DTPA grafted silica nanoparticles as bimodal-imaging contrast agents. , 2011, Biomaterials.

[65]  Haiqing Dong,et al.  Nano-assembly of bovine serum albumin driven by rare-earth-ion (Gd) biomineralization for highly efficient photodynamic therapy and tumor imaging. , 2016, Journal of materials chemistry. B.

[66]  Song Zhang,et al.  One-pot synthesis of Gd3+-functionalized gold nanoclusters for dual model (fluorescence/magnetic resonance) imaging. , 2013, Journal of materials chemistry. B.

[67]  Veit Rohde,et al.  Multiphoton excitation fluorescence microscopy of 5‐aminolevulinic acid induced fluorescence in experimental gliomas , 2008, Lasers in surgery and medicine.

[68]  X. Qu,et al.  Ultrasmall biomolecule-anchored hybrid GdVO4 nanophosphors as a metabolizable multimodal bioimaging contrast agent. , 2014, Nanoscale.

[69]  Grigory Tikhomirov,et al.  Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis. , 2014, Chemical science.

[70]  Xin-guo Jiang,et al.  Brain Delivery of NAP with PEG-PLGA Nanoparticles Modified with Phage Display Peptides , 2013, Pharmaceutical Research.

[71]  Qi Zhang,et al.  Gd complexes of diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide as a new liver-specific MRI contrast agent. , 2013, Magnetic resonance imaging.

[72]  Jianhua Hao,et al.  PEG modified BaGdF₅:Yb/Er nanoprobes for multi-modal upconversion fluorescent, in vivo X-ray computed tomography and biomagnetic imaging. , 2012, Biomaterials.

[73]  M. Botta,et al.  Selective functionalization of mesoporous silica nanoparticles with ibuprofen and Gd(III) chelates: a new probe for potential theranostic applications. , 2015, Dalton transactions.

[74]  E. Giannelis,et al.  Gd(III)-doped carbon dots as a dual fluorescent-MRI probe , 2012 .

[75]  Pius August Schubiger,et al.  Molecular imaging with PET. , 2008, Chemical reviews.

[76]  Erwin Peng,et al.  Synthesis of Water-Dispersible Gd2O3/GO Nanocomposites with Enhanced MRI T1 Relaxivity , 2015 .

[77]  H. Lusic,et al.  X-ray-computed tomography contrast agents. , 2013, Chemical reviews.

[78]  Jason J. Davis,et al.  Environmentally responsive MRI contrast agents. , 2013, Chemical communications.

[79]  Jianzhong Du,et al.  An Asymmetrical Polymer Vesicle Strategy for Significantly Improving T1 MRI Sensitivity and Cancer-Targeted Drug Delivery , 2015 .

[80]  A. Seiyama,et al.  Gd3+-functionalized near-infrared quantum dots for in vivo dual modal (fluorescence/magnetic resonance) imaging. , 2008, Chemical communications.

[81]  Hong Ding,et al.  Bioconjugation of luminescent silicon quantum dots to gadolinium ions for bioimaging applications. , 2012, Nanoscale.

[82]  Yongmin Chang,et al.  D-Glucuronic Acid Coated Gd(IO3)3·2H2O Nanomaterial as a Potential T1 MRI-CT Dual Contrast Agent , 2013 .

[83]  Yanqing Hua,et al.  A Gd-doped Mg-Al-LDH/Au nanocomposite for CT/MR bimodal imagings and simultaneous drug delivery. , 2013, Biomaterials.

[84]  Arsalan Ahmed,et al.  Fabrication and Characterization of Gd-DTPA-Loaded Chitosan-Poly(Acrylic Acid) Nanoparticles for Magnetic Resonance Imaging. , 2015, Macromolecular bioscience.

[85]  Michael J. Welch,et al.  In vivo evaluation of (64)Cu-labeled magnetic nanoparticles as a dual-modality PET/MR imaging agent. , 2010, Bioconjugate chemistry.

[86]  Hua Ai Layer-by-layer capsules for magnetic resonance imaging and drug delivery. , 2011, Advanced drug delivery reviews.

[87]  S. Eustace,et al.  Molecular and magnetic resonance imaging: The value of immunoliposomes. , 2009, Advanced drug delivery reviews.

[88]  Angelique Louie,et al.  Multimodality imaging probes: design and challenges. , 2010, Chemical reviews.

[89]  Taeghwan Hyeon,et al.  Upconverting nanoparticles: a versatile platform for wide-field two-photon microscopy and multi-modal in vivo imaging. , 2015, Chemical Society reviews.

[90]  I. Kwon,et al.  Gadolinium-coordinated elastic nanogels for in vivo tumor targeting and imaging. , 2013, Biomaterials.

[91]  P. Hermann,et al.  Gadolinium(III) complexes as MRI contrast agents: ligand design and properties of the complexes. , 2008, Dalton transactions.

[92]  Liang Yan,et al.  Recent Advances in Design and Fabrication of Upconversion Nanoparticles and Their Safe Theranostic Applications , 2013, Advanced materials.

[93]  P. Perriat,et al.  The In Vivo Radiosensitizing Effect of Gold Nanoparticles Based MRI Contrast Agents. , 2014, Small.

[94]  Daniel Citterio,et al.  Dextran Coated Gadolinium Phosphate Nanoparticles for Magnetic Resonance Tumor Imaging , 2009 .

[95]  Bingdi Chen,et al.  Bioinspired synthesis of gadolinium-based hybrid nanoparticles as MRI blood pool contrast agents with high relaxivity , 2012 .

[96]  Paul H. Holloway,et al.  GdIII‐Functionalized Fluorescent Quantum Dots as Multimodal Imaging Probes , 2006 .

[97]  N. Zhang,et al.  Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer. , 2011, Biomaterials.

[98]  Andrea Protti,et al.  Synthesis of 64CuII–Bis(dithiocarbamatebisphosphonate) and Its Conjugation with Superparamagnetic Iron Oxide Nanoparticles: In Vivo Evaluation as Dual-Modality PET–MRI Agent** , 2011, Angewandte Chemie.

[99]  S. Laurent,et al.  Micellar self-assemblies of gadolinium(III)/europium(III) amphiphilic complexes as model contrast agents for bimodal imaging. , 2014, Dalton transactions.

[100]  Qingfeng Xiao,et al.  Dual-targeting upconversion nanoprobes across the blood-brain barrier for magnetic resonance/fluorescence imaging of intracranial glioblastoma. , 2014, ACS nano.

[101]  Xing-jie Liang,et al.  Biocompatible composite nanoparticles with large longitudinal relaxivity for targeted imaging and early diagnosis of cancer. , 2013, Journal of materials chemistry. B.

[102]  Xianglong Hu,et al.  Multifunctional pH-disintegrable micellar nanoparticles of asymmetrically functionalized β-cyclodextrin-based star copolymer covalently conjugated with doxorubicin and DOTA-Gd moieties. , 2012, Biomaterials.

[103]  Carolyn R. Bertozzi,et al.  Chemical Glycobiology , 2001, Science.

[104]  T. Tachikawa,et al.  The unprecedented J-aggregate formation of rhodamine moieties induced by 9-phenylanthracenyl substitution. , 2015, Chemical communications.

[105]  Peter Caravan,et al.  Synthesis and relaxometric studies of a dendrimer-based pH-responsive MRI contrast agent. , 2008, Chemistry.

[106]  N. Logothetis,et al.  Multimodal contrast agents for in vivo neuroanatomical analysis of monosynaptic connections. , 2013, Biomaterials.

[107]  D. Astruc,et al.  Applications of vectorized gold nanoparticles to the diagnosis and therapy of cancer. , 2012, Chemical Society reviews.

[108]  Hongjie Hu,et al.  Macromolecular MRI contrast agents: Structures, properties and applications , 2013 .

[109]  M. Yokoyama,et al.  Polyion complex micelle MRI contrast agents from poly(ethylene glycol)-b-poly(l-lysine) block copolymers having Gd-DOTA; preparations and their control of T(1)-relaxivities and blood circulation characteristics. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[110]  L. Vander Elst,et al.  Assembly of near infra-red emitting upconverting nanoparticles and multiple Gd(III)-chelates as a potential bimodal contrast agent for MRI and optical imaging. , 2015, Dalton transactions.

[111]  M. Filippi,et al.  Dendrimersomes: a new vesicular nano-platform for MR-molecular imaging applications. , 2014, Chemical communications.

[112]  Jing Zhou,et al.  Gadolinium complex and phosphorescent probe-modified NaDyF4 nanorods for T1- and T2-weighted MRI/CT/phosphorescence multimodality imaging. , 2014, Biomaterials.

[113]  R. Duncan,et al.  Dendrimer biocompatibility and toxicity. , 2005, Advanced drug delivery reviews.

[114]  M. Han,et al.  Tumor targeting chitosan nanoparticles for dual-modality optical/MR cancer imaging. , 2010, Bioconjugate chemistry.

[115]  M. Reiser,et al.  Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based thermosensitive liposomes. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[116]  J. L. Turner,et al.  Synthesis of Gadolinium‐Labeled Shell‐Crosslinked Nanoparticles for Magnetic Resonance Imaging Applications , 2005 .

[117]  R. Weissleder,et al.  Imaging in the era of molecular oncology , 2008, Nature.

[118]  Biocompatible GdIII-functionalized fluorescent gold nanoclusters for optical and magnetic resonance imaging , 2013 .

[119]  Yuliang Zhao,et al.  A new near infrared photosensitizing nanoplatform containing blue-emitting up-conversion nanoparticles and hypocrellin A for photodynamic therapy of cancer cells. , 2013, Nanoscale.

[120]  Jian Zhang,et al.  Pyridine-based lanthanide complexes: towards bimodal agents operating as near infrared luminescent and MRI reporters. , 2008, Chemical communications.

[121]  H. Maeda,et al.  Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[122]  Jee-Hyun Cho,et al.  Europium-doped gadolinium sulfide nanoparticles as a dual-mode imaging agent for T1-weighted MR and photoluminescence imaging. , 2012, Biomaterials.

[123]  M. N. R. Kumar A review of chitin and chitosan applications , 2000 .

[124]  Bradley J. Beattie,et al.  89Zr-Labeled Paramagnetic Octreotide-Liposomes for PET-MR Imaging of Cancer , 2012, Pharmaceutical Research.

[125]  Hongjie Hu,et al.  Facile synthesis and in vivo evaluation of biodegradable dendritic MRI contrast agents , 2012 .

[126]  David A. Jaffray,et al.  In Vivo Performance of a Liposomal Vascular Contrast Agent for CT and MR-Based Image Guidance Applications , 2007, Pharmaceutical Research.

[127]  Jae-Chang Jung,et al.  Gd‐DOTA Conjugate of RGD as a Potential Tumor‐Targeting MRI Contrast Agent , 2008, Chembiochem : a European journal of chemical biology.

[128]  A. Tsourkas,et al.  Stabilized porous liposomes with encapsulated Gd-labeled dextran as a highly efficient MRI contrast agent. , 2014, Chemical communications.

[129]  A. Sherry,et al.  The importance of water exchange rates in the design of responsive agents for MRI. , 2013, Current opinion in chemical biology.

[130]  S. Laurent,et al.  Tuning the composition of biocompatible Gd nanohydrogels to achieve hypersensitive dual T1/T2 MRI contrast agents. , 2014, Journal of materials chemistry. B.

[131]  Linfeng Zheng,et al.  Dendrimer-Assisted Formation of Fe3O4/Au Nanocomposite Particles for Targeted Dual Mode CT/MR Imaging of Tumors. , 2015, Small.

[132]  Jun Lin,et al.  Recent progress in rare earth micro/nanocrystals: soft chemical synthesis, luminescent properties, and biomedical applications. , 2014, Chemical reviews.

[133]  Jianzhong Du,et al.  Theranostic vesicles based on bovine serum albumin and poly(ethylene glycol)-block-poly(L-lactic-co-glycolic acid) for magnetic resonance imaging and anticancer drug delivery. , 2014, Biomacromolecules.

[134]  Yanqing Hua,et al.  A NaYbF4: Tm3+ nanoprobe for CT and NIR-to-NIR fluorescent bimodal imaging. , 2012, Biomaterials.

[135]  Hao Hong,et al.  Chelator-free synthesis of a dual-modality PET/MRI agent. , 2013, Angewandte Chemie.

[136]  Wenpei Fan,et al.  Real-time in vivo quantitative monitoring of drug release by dual-mode magnetic resonance and upconverted luminescence imaging. , 2014, Angewandte Chemie.

[137]  Richey M. Davis,et al.  A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells. , 2015, Journal of the American Chemical Society.

[138]  Yu Chong,et al.  Graphene oxide based theranostic platform for T1-weighted magnetic resonance imaging and drug delivery. , 2013, ACS applied materials & interfaces.

[139]  F. Hübner,et al.  Detection of hepatocellular carcinoma in transgenic mice by Gd-DTPA- and rhodamine 123-conjugated human serum albumin nanoparticles in T1 magnetic resonance imaging. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[140]  Peiqi Zhao,et al.  Multifunctional Nanoparticles Composed of A Poly( dl‐lactide‐coglycolide) Core and A Paramagnetic Liposome Shell for Simultaneous Magnetic Resonance Imaging and Targeted Therapeutics , 2011 .

[141]  Marie C. Heffern,et al.  Lanthanide probes for bioresponsive imaging. , 2014, Chemical reviews.

[142]  E. Terreno,et al.  Supramolecular protamine/Gd-loaded liposomes adducts as relaxometric protease responsive probes. , 2011, Bioorganic & medicinal chemistry.

[143]  Xiaogang Qu,et al.  Long-circulating Gd(2)O(3):Yb(3+), Er(3+) up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging. , 2013, Biomaterials.

[144]  Zhuang Liu,et al.  Photosensitizer-Conjugated Albumin-Polypyrrole Nanoparticles for Imaging-Guided In Vivo Photodynamic/Photothermal Therapy. , 2015, Small.

[145]  R. Zhang,et al.  The degradation and clearance of Poly(N-hydroxypropyl-L-glutamine)-DTPA-Gd as a blood pool MRI contrast agent. , 2012, Biomaterials.

[146]  Ambika Bumb,et al.  Macromolecules, dendrimers, and nanomaterials in magnetic resonance imaging: the interplay between size, function, and pharmacokinetics. , 2010, Chemical reviews.

[147]  K. Hong,et al.  Cu(2+)-responsive bimodal (optical/MRI) contrast agent for cellular imaging. , 2013, Organic letters.

[148]  W. Xu,et al.  Dextran Gadolinium Complexes as Contrast Agents for Magnetic Resonance Imaging to Sentinel Lymph Nodes , 2010, Pharmaceutical Research.

[149]  S. Laurent,et al.  Polymer–gold nanohybrids with potential use in bimodal MRI/CT: enhancing the relaxometric properties of Gd(III) complexes , 2012 .

[150]  Chang-Tong Yang,et al.  Gd(III) chelates for MRI contrast agents: from high relaxivity to “smart”, from blood pool to blood–brain barrier permeable , 2012 .

[151]  W. Marsden I and J , 2012 .

[152]  Yanqing Hua,et al.  Multifunctional nanoprobes for upconversion fluorescence, MR and CT trimodal imaging. , 2012, Biomaterials.

[153]  Nengqin Jia,et al.  Regulation of multifunctional mesoporous core-shell nanoparticles with luminescence and magnetic properties for biomedical applications. , 2014, Journal of materials chemistry. B.

[154]  E. Terreno,et al.  Improved paramagnetic liposomes for MRI visualization of pH triggered release. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[155]  Andrew G. Glen,et al.  APPL , 2001 .

[156]  L. Tei,et al.  Tuning glutamine binding modes in Gd-DOTA-based probes for an improved MRI visualization of tumor cells. , 2009, Chemistry.

[157]  Minoru Suzuki,et al.  Gadolinium-loaded chitosan nanoparticles for neutron-capture therapy: Influence of micrometric properties of the nanoparticles on tumor-killing effect. , 2014, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[158]  Christophe Dujardin,et al.  Modelling energy deposition in nanoscintillators to predict the efficiency of the X-ray-induced photodynamic effect. , 2015, Nanoscale.

[159]  E. Gianolio,et al.  Relaxometric investigations and MRI evaluation of a liposome-loaded pH-responsive gadolinium(III) complex. , 2012, Inorganic chemistry.

[160]  M. D. Rowe,et al.  Polymer-modified gadolinium metal-organic framework nanoparticles used as multifunctional nanomedicines for the targeted imaging and treatment of cancer. , 2009, Biomacromolecules.

[161]  R. Gullapalli,et al.  HPMA copolymer-doxorubicin-gadolinium conjugates: synthesis, characterization, and in vitro evaluation. , 2008, Macromolecular bioscience.

[162]  Wei-Ting Huang,et al.  Gadolinium-based CuInS2/ZnS nanoprobe for dual-modality magnetic resonance/optical imaging. , 2013, ACS applied materials & interfaces.

[163]  Kwangmeyung Kim,et al.  Hyaluronic acid-ceramide-based optical/MR dual imaging nanoprobe for cancer diagnosis. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[164]  Qian Liu,et al.  18F-Labeled magnetic-upconversion nanophosphors via rare-Earth cation-assisted ligand assembly. , 2011, ACS nano.

[165]  P. Chandrasekharan,et al.  Single molecular hyperbranched nanoprobes for fluorescence and magnetic resonance dual modal imaging , 2013 .

[166]  Mingwu Shen,et al.  Computed tomography imaging of cancer cells using acetylated dendrimer-entrapped gold nanoparticles. , 2011, Biomaterials.

[167]  G. Yahioglu,et al.  Modern bioassays using metal chelates as luminescent probes. , 1996, Natural product reports.

[168]  É. Tóth,et al.  Rotational dynamics account for pH-dependent relaxivities of PAMAM dendrimeric, Gd-based potential MRI contrast agents. , 2005, Chemistry.

[169]  Jian Luo,et al.  A Gd3Al tetranuclear complex as a potential bimodal MRI/optical imaging agent. , 2012, Dalton transactions.

[170]  Chunru Wang,et al.  Multifunctional imaging probe based on gadofulleride nanoplatform. , 2012, Nanoscale.

[171]  Wei Feng,et al.  Upconversion‐Nanophosphor‐Based Functional Nanocomposites , 2013, Advanced materials.

[172]  F. Hirayama,et al.  X-ray crystallographic characterization of nilvadipine monohydrate and its phase transition behavior. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[173]  S. Laurent,et al.  Macromolecular Ligands for Gadolinium MRI Contrast Agents , 2012 .

[174]  Shan Jiang,et al.  Multicolor Core/Shell‐Structured Upconversion Fluorescent Nanoparticles , 2008 .

[175]  J. Martinelli,et al.  Cleavable β-cyclodextrin nanocapsules incorporating Gd(III)-chelates as bioresponsive MRI probes. , 2011, Chemical communications.

[176]  Xiaolong Liang,et al.  PEGylated Polypyrrole Nanoparticles Conjugating Gadolinium Chelates for Dual‐Modal MRI/Photoacoustic Imaging Guided Photothermal Therapy of Cancer , 2015 .

[177]  Mingwu Shen,et al.  PEGylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography. , 2012, Biomaterials.

[178]  F. Fang,et al.  An ultrasmall and metabolizable PEGylated NaGdF4:Dy nanoprobe for high-performance T(1)/T(2)-weighted MR and CT multimodal imaging. , 2015, Nanoscale.

[179]  P. Chu,et al.  Recent advances in multifunctional magnetic nanoparticles and applications to biomedical diagnosis and treatment , 2013 .

[180]  Yi Liu,et al.  Water-solubility of chitosan and its antimicrobial activity , 2006 .

[181]  Mauro Ferrari,et al.  Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast , 2010, Nature nanotechnology.

[182]  R. Dacosta,et al.  A multifunctional polymeric nanotheranostic system delivers doxorubicin and imaging agents across the blood-brain barrier targeting brain metastases of breast cancer. , 2014, ACS nano.

[183]  Zhen Cheng,et al.  Hybrid Nanotrimers for Dual T1 and T2-Weighted Magnetic Resonance Imaging , 2014, ACS nano.

[184]  Jun Ling,et al.  Novel lanthanide–polymer complexes for dye-free dual modal probes for MRI and fluorescence imaging , 2015 .

[185]  P. Prasad,et al.  Upconversion Nanoparticles: Design, Nanochemistry, and Applications in Theranostics , 2014, Chemical reviews.

[186]  S. Luo,et al.  Inorganic photosensitizer coupled Gd-based upconversion luminescent nanocomposites for in vivo magnetic resonance imaging and near-infrared-responsive photodynamic therapy in cancers. , 2015, Biomaterials.

[187]  Dongmei Yang,et al.  Ultra-small BaGdF5-based upconversion nanoparticles as drug carriers and multimodal imaging probes. , 2014, Biomaterials.

[188]  J. Newcombe,et al.  Detection of choline transporter‐like 1 protein CTL1 in neuroblastoma × glioma cells and in the CNS, and its role in choline uptake , 2009, Journal of neurochemistry.

[189]  Dongmei Wu,et al.  Paramagnetic hollow silica nanospheres for in vivo targeted ultrasound and magnetic resonance imaging. , 2014, Biomaterials.

[190]  Andrew Tsourkas,et al.  Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent. , 2010, Angewandte Chemie.

[191]  Fabao Gao,et al.  Multifunctional nanoprobe for MRI/optical dual-modality imaging and radical scavenging. , 2013, Chemistry.

[192]  Chengjie Sun,et al.  A multiple gadolinium complex decorated fullerene as a highly sensitive T(1) contrast agent. , 2015, Chemical communications.

[193]  G. Rutter,et al.  Lanthanide(III) Complexes of Rhodamine–DO3A Conjugates as Agents for Dual-Modal Imaging , 2013, Inorganic chemistry.

[194]  Wei Feng,et al.  Gd3+ complex-modified NaLuF4-based upconversion nanophosphors for trimodality imaging of NIR-to-NIR upconversion luminescence, X-Ray computed tomography and magnetic resonance. , 2012, Biomaterials.

[196]  D. Talham,et al.  One-step synthesis of gradient gadolinium ironhexacyanoferrate nanoparticles: a new particle design easily combining MRI contrast and photothermal therapy. , 2015, Nanoscale.

[197]  R. Sze,et al.  Biofunctionalized gadolinium-containing prussian blue nanoparticles as multimodal molecular imaging agents. , 2014, Bioconjugate chemistry.

[198]  A. Tsourkas,et al.  Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments. , 2013, Journal of medicinal chemistry.

[199]  Hung-Wei Yang,et al.  Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging. , 2014, Biomaterials.

[200]  R. Gullapalli,et al.  Macrophage targeted N-(2-hydroxypropyl)methacrylamide conjugates for magnetic resonance imaging. , 2006, Molecular pharmaceutics.

[201]  D. Wilbur,et al.  Radiohalogens for imaging and therapy. , 2005, Chemical Society reviews.

[202]  R. Jacobs,et al.  Multimodality PET/MRI agents targeted to activated macrophages , 2013, JBIC Journal of Biological Inorganic Chemistry.

[203]  C. Anderson,et al.  Coordinating radiometals of copper, gallium, indium, yttrium, and zirconium for PET and SPECT imaging of disease. , 2010, Chemical reviews.

[204]  Ping Hu,et al.  Tetranuclear gadolinium(III) porphyrin complex as a theranostic agent for multimodal imaging and photodynamic therapy. , 2014, Inorganic chemistry.

[205]  Yun Sun,et al.  Dual-modality in vivo imaging using rare-earth nanocrystals with near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence and magnetic resonance properties. , 2010, Biomaterials.

[206]  Yuliang Zhao,et al.  Smart Albumin‐Biomineralized Nanocomposites for Multimodal Imaging and Photothermal Tumor Ablation , 2015, Advanced materials.

[207]  J. M. de la Fuente,et al.  Synthesis and properties of multifunctional tetragonal Eu:GdPO4 nanocubes for optical and magnetic resonance imaging applications. , 2013, Inorganic chemistry.

[208]  Yunlong Deng,et al.  T1-T2 dual-modal MRI of brain gliomas using PEGylated Gd-doped iron oxide nanoparticles. , 2014, Journal of colloid and interface science.

[209]  Weisheng Liu,et al.  Two-photon sensitized hollow Gd2O3:Eu(3+) nanocomposites for real-time dual-mode imaging and monitoring of anticancer drug release. , 2016, Chemical communications.

[210]  D. Rhodes,et al.  Superconductivity with extremely large upper critical fields in Nb$_{2}$Pd$_{0.81}$S$_{5}$ , 2013 .

[211]  F. Arena,et al.  Gd-AAZTA-MADEC, an improved blood pool agent for DCE-MRI studies on mice on 1 T scanners. , 2016, Biomaterials.

[212]  Jiechao Ge,et al.  Multifunctional gadofulleride nanoprobe for magnetic resonance imaging/fluorescent dual modality molecular imaging and free radical scavenging , 2013 .

[213]  D. K. Yi,et al.  A study of Gd loaded silica nanoparticles for both optical and magnetic resonance imaging of cells , 2013 .

[214]  B. Liu,et al.  Hyperbranched conjugated polyelectrolyte for dual-modality fluorescence and magnetic resonance cancer imaging. , 2012, Small.

[215]  Yuan Yuan,et al.  Supramolecular aggregates from polyacrylates and Gd(III)-containing cationic surfactants as high-relaxivity MRI contrast agents , 2015 .