Radiolabelled Polymeric Materials for Imaging and Treatment of Cancer: Quo Vadis?

Owing to their tunable blood circulation time and suitable plasma stability, polymer-based nanomaterials hold a great potential for designing and utilising multifunctional nanocarriers for efficient imaging and effective treatment of cancer. When tagged with appropriate radionuclides, they may allow for specific detection (diagnosis) as well as the destruction of tumours (therapy) or even customization of materials, aiming to both diagnosis and therapy (theranostic approach). This review provides an overview of recent developments of radiolabelled polymeric nanomaterials (natural and synthetic polymers) for molecular imaging of cancer, specifically, applying nuclear techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Different approaches to radiolabel polymers are evaluated from the methodical radiochemical point of view. This includes new bifunctional chelating agents (BFCAs) for radiometals as well as novel labelling methods. Special emphasis is given to eligible strategies employed to evade the mononuclear phagocytic system (MPS) in view of efficient targeting. The discussion encompasses promising strategies currently employed as well as emerging possibilities in radionuclide-based cancer therapy. Key issues involved in the clinical translation of radiolabelled polymers and future scopes of this intriguing research field are also discussed.

[1]  M. Ross,et al.  A Phase 2 Study of 99mTc-Tilmanocept in the Detection of Sentinel Lymph Nodes in Melanoma and Breast Cancer , 2011, Annals of Surgical Oncology.

[2]  M. Woodle,et al.  New amphipatic polymer-lipid conjugates forming long-circulating reticuloendothelial system-evading liposomes. , 1994, Bioconjugate chemistry.

[3]  P. Erba,et al.  Towards the use of nanoparticles in cancer therapy and imaging. , 2007, Drug news & perspectives.

[4]  Stavroula Sofou,et al.  Enhanced loading efficiency and retention of 225Ac in rigid liposomes for potential targeted therapy of micrometastases. , 2008, Bioconjugate chemistry.

[5]  J. Davies,et al.  Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470 , 2004, Nature Medicine.

[6]  U. Haberkorn,et al.  Conjugation of DOTA using isolated phenolic active esters: the labeling and biodistribution of albumin as blood pool marker. , 2005, Bioconjugate chemistry.

[7]  Chris Orvig,et al.  Matching chelators to radiometals for radiopharmaceuticals. , 2014, Chemical Society reviews.

[8]  Ryan M. Pearson,et al.  Poly(ethylene glycol) Corona Chain Length Controls End-Group-Dependent Cell Interactions of Dendron Micelles , 2014, Macromolecules.

[9]  J. Steinbach,et al.  Hexadentate bispidine derivatives as versatile bifunctional chelate agents for copper(II) radioisotopes. , 2009, Bioconjugate chemistry.

[10]  Leaf Huang,et al.  Nanoparticles evading the reticuloendothelial system: role of the supported bilayer. , 2009, Biochimica et biophysica acta.

[11]  K. Ulbrich,et al.  Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[12]  R. Mülhaupt,et al.  Controlled Synthesis of Hyperbranched Polyglycerols by Ring-Opening Multibranching Polymerization , 1999 .

[13]  Hwan-Jeong Jeong,et al.  Local Retention and Combination Effects of Biocompatible Doxorubicin-Loaded and Radioiodine-Labeled Microhydrogels in Cancer Therapy. , 2014, ACS macro letters.

[14]  S. Nilsson,et al.  99mTc-dextran-antibody conjugates. Labelling procedures. , 1996, Acta oncologica.

[15]  Jayant Khandare,et al.  Multifunctional dendritic polymers in nanomedicine: opportunities and challenges. , 2012, Chemical Society reviews.

[16]  Felix Kratz,et al.  Impact of albumin on drug delivery--new applications on the horizon. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[17]  V. Préat,et al.  PLGA-based nanoparticles: an overview of biomedical applications. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[18]  Triantafyllos Stylianopoulos,et al.  Design considerations for nanotherapeutics in oncology. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[19]  A. Kassis Cancer therapy with Auger electrons: are we almost there? , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  Martin W. Brechbiel,et al.  Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity , 2000, European Journal of Nuclear Medicine.

[21]  H. Maecke,et al.  Radiopharmaceutical development of radiolabelled peptides , 2012, European Journal of Nuclear Medicine and Molecular Imaging.

[22]  Oliver Thews,et al.  Radioactive labeling of defined HPMA-based polymeric structures using [18F]FETos for in vivo imaging by positron emission tomography. , 2009, Biomacromolecules.

[23]  C. Hoh,et al.  A preclinical study of prostate sentinel lymph node mapping with [99mTC]diethylenetetramine pentaacetic acid-mannosyl-dextran. , 2006, The Journal of urology.

[24]  R. Haag,et al.  Shell Cleavable Dendritic Polyglycerol Sulfates Show High Anti‐Inflammatory Properties by Inhibiting L‐Selectin Binding and Complement Activation , 2015, Advanced healthcare materials.

[25]  Munir Ahmad,et al.  Studying the biological feasibility of [99mTc(CO)3]-dextran-cysteine-cysteine-mannose as a potential molecular radiopharmaceutical for sentinel node detection , 2014, Annals of Nuclear Medicine.

[26]  D. Kuhl,et al.  Tc-99m dextran: a new blood-pool-labeling agent for radionuclide angiocardiography. , 1982, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  Linqi Shi,et al.  Synthesis, biodistribution, and imaging of PEGylated-acetylated polyamidoamine dendrimers. , 2014, Journal of nanoscience and nanotechnology.

[28]  T Lammers,et al.  Tumour-targeted nanomedicines: principles and practice , 2008, British Journal of Cancer.

[29]  Victor Malgras,et al.  Multi-Stimuli-Responsive Polymeric Materials. , 2015, Chemistry.

[30]  K. Pitman,et al.  [99mTc]Tilmanocept Accurately Detects Sentinel Lymph Nodes and Predicts Node Pathology Status in Patients with Oral Squamous Cell Carcinoma of the Head and Neck: Results of a Phase III Multi-institutional Trial , 2015, Annals of Surgical Oncology.

[31]  A. Fischman,et al.  Indium-111 DTPA-heparin: radiolabeling, pharmacokinetics, and biodistribution following intravenous administration in rat and rabbit. , 1998, Thrombosis research.

[32]  Vasudha Sundram,et al.  Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth , 2010, Journal of ovarian research.

[33]  H. Hong,et al.  Image-Guided Drug Delivery with Single-Photon Emission Computed Tomography: A Review of Literature. , 2015, Current drug targets.

[34]  C. Hoh,et al.  [(99m)Tc]MAG(3)-mannosyl-dextran: a receptor-binding radiopharmaceutical for sentinel node detection. , 2001, Nuclear medicine and biology.

[35]  A. Mintz,et al.  Molecular targeted α-particle therapy for oncologic applications. , 2014, AJR. American journal of roentgenology.

[36]  S. Stroobants,et al.  μPET imaging of the pharmacokinetic behavior of medium and high molar mass (89)Zr-labeled poly(2-ethyl-2-oxazoline) in comparison to poly(ethylene glycol). , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[37]  Warren C W Chan,et al.  The effect of nanoparticle size, shape, and surface chemistry on biological systems. , 2012, Annual review of biomedical engineering.

[38]  C. Kojima,et al.  Dendrimers for theranostic applications , 2015, Biomolecular concepts.

[39]  Jun Wang,et al.  Smart Superstructures with Ultrahigh pH-Sensitivity for Targeting Acidic Tumor Microenvironment: Instantaneous Size Switching and Improved Tumor Penetration. , 2016, ACS nano.

[40]  Jinhua Zhao,et al.  Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas. , 2015, ACS applied materials & interfaces.

[41]  J. Valliant,et al.  Synthesis, Radiolabeling, and In Vivo Imaging of PEGylated High-Generation Polyester Dendrimers. , 2015, Biomacromolecules.

[42]  Dalong Ni,et al.  Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence. , 2015, Angewandte Chemie.

[43]  Ronnie H. Fang,et al.  Lipid- and Polymer-Based Nanostructures for Cancer Theranostics , 2012, Theranostics.

[44]  H. Maecke,et al.  Radiolabeled Peptides: Valuable Tools for the Detection and Treatment of Cancer , 2012, Theranostics.

[45]  J. Kotzerke,et al.  A kit for labeling of [188Re] human serum albumin microspheres for therapeutic use in nuclear medicine. , 2005, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

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

[47]  Meliha Ekinci,et al.  Methotrexate loaded chitosan nanoparticles: Preparation, radiolabeling and in vitro evaluation for breast cancer diagnosis , 2015 .

[48]  S. Sarkar,et al.  Noninvasive Imaging of Liposomal Delivery of Superparamagnetic Iron Oxide Nanoparticles to Orthotopic Human Breast Tumor in Mice , 2015, Pharmaceutical Research.

[49]  P. Bartenstein,et al.  Multimerization of cRGD Peptides by Click Chemistry: Synthetic Strategies, Chemical Limitations, and Influence on Biological Properties , 2010, Chembiochem : a European journal of chemical biology.

[50]  R. Zhang,et al.  Indium-based and iodine-based labeling of HPMA copolymer-epirubicin conjugates: Impact of structure on the in vivo fate. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[51]  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.

[52]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[53]  Hwan-Jeong Jeong,et al.  The Alginate Layer for Improving Doxorubicin Release and Radiolabeling Stability of Chitosan Hydrogels , 2015, Nuclear Medicine and Molecular Imaging.

[54]  T. Cham,et al.  On-site preparation of technetium-99m labeled human serum albumin for clinical application. , 2007, The Tohoku journal of experimental medicine.

[55]  A. Perkins,et al.  Preparation of Tc-99m-macroaggregated albumin from recombinant human albumin for lung perfusion imaging. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[56]  Shraddha S. Nigavekar,et al.  Fabrication of {198Au0} radioactive composite nanodevices and their use for nanobrachytherapy. , 2008, Nanomedicine : nanotechnology, biology, and medicine.

[57]  Jan C M van Hest,et al.  Stimuli-responsive polymersomes and nanoreactors. , 2016, Journal of materials chemistry. B.

[58]  D. Häussinger,et al.  An octadentate bifunctional chelating agent for the development of stable zirconium-89 based molecular imaging probes. , 2014, Chemical communications.

[59]  J. Au,et al.  Tumor Priming Enhances Delivery and Efficacy of Nanomedicines , 2007, Journal of Pharmacology and Experimental Therapeutics.

[60]  K. Edwards,et al.  Nuclisome: a novel concept for radionuclide therapy using targeting liposomes , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[61]  Jyothi U. Menon,et al.  Polymeric nanoparticles for targeted radiosensitization of prostate cancer cells. , 2015, Journal of biomedical materials research. Part A.

[62]  S. Bhattacharyya,et al.  Metallic radionuclides in the development of diagnostic and therapeutic radiopharmaceuticals. , 2011, Dalton transactions.

[63]  H. Lundqvist,et al.  Experimental Radionuclide Therapy of HER2-Expressing Xenografts Using Two-Step Targeting Nuclisome Particles , 2012, The Journal of Nuclear Medicine.

[64]  G. Loudos,et al.  Preliminary evaluation of a 99mTc labeled hybrid nanoparticle bearing a cobalt ferrite core: in vivo biodistribution. , 2012, Journal of Biomedical Nanotechnology.

[65]  Z. Liu,et al.  Development of RGD-based radiotracers for tumor imaging and therapy: translating from bench to bedside. , 2013, Current molecular medicine.

[66]  Shaoyi Jiang,et al.  Nanoparticles for drug delivery prepared from amphiphilic PLGA zwitterionic block copolymers with sharp contrast in polarity between two blocks. , 2010, Angewandte Chemie.

[67]  D. Lee,et al.  Preparation of 18F-human serum albumin: a simple and efficient protein labeling method with 18F using a hydrazone-formation method. , 2005, Bioconjugate chemistry.

[68]  Felix Kratz,et al.  Polymer therapeutics: concepts and applications. , 2006, Angewandte Chemie.

[69]  P. Choyke,et al.  Super enhanced permeability and retention (SUPR) effects in tumors following near infrared photoimmunotherapy. , 2016, Nanoscale.

[70]  H. Wester,et al.  A shortcut to high-affinity Ga-68 and Cu-64 radiopharmaceuticals: one-pot click chemistry trimerisation on the TRAP platform. , 2015, Dalton transactions.

[71]  K. Syrigos,et al.  Influence of tumour size on uptake of111In-DTPA-labelled pegylated liposomes in a human tumour xenograft model , 2000, British Journal of Cancer.

[72]  J. Kučka,et al.  Biodistribution of a radiolabelled thermoresponsive polymer in mice. , 2010, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[73]  G. Wei,et al.  Roles of dextrans on improving lymphatic drainage for liposomal drug delivery system , 2010, Journal of drug targeting.

[74]  A. Sargeson,et al.  Synthesis of a new cage ligand, SarAr, and its complexation with selected transition metal ions for potential use in radioimaging , 2001 .

[75]  B. Rehm Bacterial polymers: biosynthesis, modifications and applications , 2010, Nature Reviews Microbiology.

[76]  W. Cai,et al.  64Cu-Labeled Tetrameric and Octameric RGD Peptides for Small-Animal PET of Tumor αvβ3 Integrin Expression , 2007, Journal of Nuclear Medicine.

[77]  R. Haag,et al.  Dendritic polyglycerol: a new versatile biocompatible-material. , 2002, Journal of biotechnology.

[78]  Hsiu-yu Chang,et al.  The novel preparation of 99mTc(I)-labeled human serum albumin (HSA) nanoparticles as a SPECT imaging agent , 2015, Journal of Radioanalytical and Nuclear Chemistry.

[79]  J. Varshosaz Dextran conjugates in drug delivery , 2012, Expert opinion on drug delivery.

[80]  D. Hellwig,et al.  [Nuclear Medicine in Germany. Key data from official statistics]. , 2011, Nuklearmedizin. Nuclear medicine.

[81]  Jason E Gestwicki,et al.  Synthetic multivalent ligands as probes of signal transduction. , 2006, Angewandte Chemie.

[82]  Zhen Cheng,et al.  Radiolabeled affibody-albumin bioconjugates for HER2-positive cancer targeting. , 2011, Bioconjugate chemistry.

[83]  S. Ametamey,et al.  (64)Cu- and (68)Ga-Based PET Imaging of Folate Receptor-Positive Tumors: Development and Evaluation of an Albumin-Binding NODAGA-Folate. , 2016, Molecular pharmaceutics.

[84]  R. Satchi‐Fainaro Targeting Tumor Vasculature: Reality or a Dream? , 2002, Journal of drug targeting.

[85]  R. Haag,et al.  5. Multifunctional Polymer Architectures , 2016 .

[86]  C K Hoh,et al.  A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[87]  S. Subramanian,et al.  Studies toward the biological efficacy of (99m)Tc-labeled dextran-cysteine-mannose ([(99m)Tc(CO)(3)]DCM20) for sentinel lymph node detection. , 2012, Cancer biotherapy & radiopharmaceuticals.

[88]  M. Subbarayan,et al.  Water-soluble 99mTc-labeled dendritic novel porphyrins tumor imaging and diagnosis. , 2001, Biochemical and biophysical research communications.

[89]  M. Béhé,et al.  Radioiodination of monoclonal antibodies, proteins and peptides for diagnosis and therapy , 2002, Nuklearmedizin.

[90]  J. Papadimitriou,et al.  Polymer-peptide conjugates for angiogenesis targeted tumor radiotherapy. , 2006, Nuclear medicine and biology.

[91]  E. W. Meijer,et al.  Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[92]  T. Saba Physiology and physiopathology of the reticuloendothelial system. , 1970, Archives of internal medicine.

[93]  Jinwoo Cheon,et al.  Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology. , 2008, Accounts of chemical research.

[94]  P. Cullis,et al.  Drug Delivery Systems: Entering the Mainstream , 2004, Science.

[95]  D. Yan,et al.  Dendritic Polymers for Theranostics , 2016, Theranostics.

[96]  S. Gambhir,et al.  microPET Imaging of Glioma Integrin αvβ3 Expression Using 64Cu-Labeled Tetrameric RGD Peptide , 2005 .

[97]  J. Bunnett Mechanism and reactivity in aromatic nucleophilic substitution reactions , 1958 .

[98]  S. Buchwald,et al.  Copper-catalyzed halogen exchange in aryl halides: an aromatic Finkelstein reaction. , 2002, Journal of the American Chemical Society.

[99]  S. Nilsson,et al.  The potential of radiolabeled EGF‐dextran conjugates in the treatment of urinary bladder carcinoma , 1997, Cancer.

[100]  James D Bryers,et al.  Zwitterionic carboxybetaine polymer surfaces and their resistance to long-term biofilm formation. , 2009, Biomaterials.

[101]  D. Hanahan,et al.  Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice. , 1998, The Journal of clinical investigation.

[102]  D. Scheinberg,et al.  Enhanced Retention of the α-Particle-Emitting Daughters of Actinium-225 by Liposome Carriers , 2007 .

[103]  J. Correia,et al.  Radiolabeled mannosylated dextran derivatives bearing an NIR-fluorophore for sentinel lymph node imaging. , 2014, Bioconjugate chemistry.

[104]  H. Afarideh,et al.  Radio-immunoconjugated, Dox-loaded, surface-modified superparamagnetic iron oxide nanoparticles (SPIONs) as a bioprobe for breast cancer tumor theranostics , 2014, Journal of Radioanalytical and Nuclear Chemistry.

[105]  J. Fréchet,et al.  Dendrimers and Other Dendritic Polymers: Frechet/Dendrimers , 2001 .

[106]  Wilbur Ds Radiohalogenation of proteins: An overview of radionuclides, labeling methods and reagents for conjugate labeling , 1992 .

[107]  K. Ulbrich,et al.  Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers. , 2009, Biomaterials.

[108]  Anne L. van de Ven,et al.  Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. , 2013, Nature nanotechnology.

[109]  David E Reichert,et al.  Microfluidic radiolabeling of biomolecules with PET radiometals. , 2013, Nuclear medicine and biology.

[110]  K. Mardon,et al.  Synthesis of a multimodal molecular imaging probe based on a hyperbranched polymer architecture , 2014 .

[111]  Jyothi,et al.  Preparation and Characterization of 125I Labeled Bovine Serum Albumin , 2015, Indian Journal of Pharmaceutical Sciences.

[112]  O. Prante,et al.  PET Radiopharmaceuticals for Imaging Integrin Expression: Tracers in Clinical Studies and Recent Developments , 2014, BioMed research international.

[113]  J. Park,et al.  Stimuli-responsive polymersomes for cancer therapy. , 2016, Biomaterials science.

[114]  Xinrong Liu,et al.  Synthesis and in vitro characterization of a dendrimer-MORF conjugate for amplification pretargeting. , 2008, Bioconjugate chemistry.

[115]  D. Kerr,et al.  Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[116]  H. Wester,et al.  A Practical Guide on the Synthesis of Metal Chelates for Molecular Imaging and Therapy by Means of Click Chemistry. , 2016, Chemistry.

[117]  Shaoyi Jiang,et al.  Ultralow‐Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications , 2010, Advanced materials.

[118]  Fuping Gao,et al.  Ultrasmall [(64)Cu]Cu nanoclusters for targeting orthotopic lung tumors using accurate positron emission tomography imaging. , 2015, ACS nano.

[119]  R. Bergmann,et al.  Comparison of the stability of Y-90-, Lu-177- and Ga-68- labeled human serum albumin microspheres (DOTA-HSAM). , 2010, Nuclear medicine and biology.

[120]  V. Torchilin,et al.  Enhanced tumor visualization by gamma-scintigraphy with 111In-labeled polychelating-polymer-containing immunoliposomes. , 2006, Molecular pharmaceutics.

[121]  K. Syrigos,et al.  Biodistribution and pharmacokinetics of111In-DTPA-labelled pegylated liposomes in a human tumour xenograft model: implications for novel targeting strategies , 2000, British Journal of Cancer.

[122]  K. Ulbrich,et al.  Fine tuning of the pH-dependent drug release rate from polyHPMA-ellipticinium conjugates. , 2013, Bioorganic & medicinal chemistry.

[123]  C. Hoh,et al.  Lymphoseek: A Molecular Radiopharmaceutical for Sentinel Node Detection , 2003, Annals of Surgical Oncology.

[124]  Yanqing Hua,et al.  A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy. , 2013, Journal of the American Chemical Society.

[125]  A. Beck‐Sickinger,et al.  Targeted tumor diagnosis and therapy with peptide hormones as radiopharmaceuticals. , 2008, Anti-cancer agents in medicinal chemistry.

[126]  K. Ulbrich,et al.  Image-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy , 2008, British Journal of Cancer.

[127]  G. Luker,et al.  Targeted non-covalent self-assembled nanoparticles based on human serum albumin. , 2012, Biomaterials.

[128]  C. Orvig,et al.  Tumour targeting with radiometals for diagnosis and therapy. , 2013, Chemical communications.

[129]  N. O’Brien-Simpson,et al.  Antibiofouling polymer interfaces: poly(ethylene glycol) and other promising candidates , 2015 .

[130]  Jason S. Lewis,et al.  Unconventional Nuclides for Radiopharmaceuticals , 2010, Molecular imaging.

[131]  Helmut Ringsdorf,et al.  Polymer therapeutics—polymers as drugs, drug and protein conjugates and gene delivery systems: Past, present and future opportunities* , 2006, Journal of drug targeting.

[132]  T Lammers,et al.  Applications of nanoparticles for diagnosis and therapy of cancer. , 2015, The British journal of radiology.

[133]  Tang Yang,et al.  Preparation and distribution of 5-fluorouracil (125)I sodium alginate-bovine serum albumin nanoparticles. , 1999, World journal of gastroenterology.

[134]  S. Nilsson,et al.  Biodistribution, blood half-life, and receptor binding of a somatostatin-dextran conjugate , 2001, Medical oncology.

[135]  C. Hoh,et al.  Dose-dependent biodistribution of [(99m)Tc]DTPA-mannosyl-dextran for breast cancer sentinel lymph node mapping. , 2003, Nuclear medicine and biology.

[136]  Ronald C. Chen,et al.  Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the treatment of ovarian cancer peritoneal metastasis. , 2011, Biomaterials.

[137]  Madhavan Nallani,et al.  Biohybrid polymer capsules. , 2009, Chemical reviews.

[138]  K. Ulbrich,et al.  Effect of radiotherapy and hyperthermia on the tumor accumulation of HPMA copolymer-based drug delivery systems. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[139]  Mauro Ferrari,et al.  Nanomedicine--challenge and perspectives. , 2009, Angewandte Chemie.

[140]  Chun Li,et al.  A targeted approach to cancer imaging and therapy. , 2014, Nature materials.

[141]  K Togashi,et al.  Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[142]  Mauro Ferrari,et al.  Principles of nanoparticle design for overcoming biological barriers to drug delivery , 2015, Nature Biotechnology.

[143]  R. J. Alves,et al.  Radiolabeling of low molecular weight d-galactose-based glycodendrimer with technetium-99m and biodistribution studies , 2013, Journal of Radioanalytical and Nuclear Chemistry.

[144]  C. Hoh,et al.  Sentinel lymph node mapping of breast cancer via intradermal administration of Lymphoseek. , 2007, Nuclear medicine and biology.

[145]  K. Yadav,et al.  Long circulating nanoparticles of etoposide using PLGA‐MPEG and PLGA‐pluronic block copolymers: characterization, drug‐release, blood‐clearance, and biodistribution studies , 2010 .

[146]  Silvia Muro,et al.  Endothelial targeting of polymeric nanoparticles stably labeled with the PET imaging radioisotope iodine-124. , 2012, Biomaterials.

[147]  D. Shabat,et al.  Self-immolative dendrimers: A distinctive approach to molecular amplification , 2010 .

[148]  D. Anjum,et al.  In vivo evaluation of the biodistribution of intravenously administered naked and functionalised silver nanoparticles in rabbit. , 2015, IET nanobiotechnology.

[149]  S. Nilsson,et al.  Radiolabeling of dextran with rhenium-188. , 2000, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[150]  M. Schwaiger,et al.  EGFR-Targeted Adenovirus Dendrimer Coating for Improved Systemic Delivery of the Theranostic NIS Gene , 2013, Molecular therapy. Nucleic acids.

[151]  T. Teknos,et al.  Use of a novel receptor-targeted (CD206) radiotracer, 99mTc-tilmanocept, and SPECT/CT for sentinel lymph node detection in oral cavity squamous cell carcinoma: initial institutional report in an ongoing phase 3 study. , 2013, JAMA otolaryngology-- head & neck surgery.

[152]  M. Uesaka,et al.  Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. , 2011, Nature nanotechnology.

[153]  C. R. Leemans,et al.  Improved tumor targeting of anti–epidermal growth factor receptor Nanobodies through albumin binding: taking advantage of modular Nanobody technology , 2008, Molecular Cancer Therapeutics.

[154]  Raimo Hartmann,et al.  In vivo integrity of polymer-coated gold nanoparticles. , 2015, Nature nanotechnology.

[155]  Remo Guidieri Res , 1995, RES: Anthropology and Aesthetics.

[156]  J. Correia,et al.  New (99m)Tc(CO)(3) mannosylated dextran bearing S-derivatized cysteine chelator for sentinel lymph node detection. , 2012, Molecular pharmaceutics.

[157]  S. Nilsson,et al.  Labeling of polypeptides with technetium-99m using a dextran spacer. , 1995, Cancer research.

[158]  Monica Shokeen,et al.  Biodegradable dendritic positron-emitting nanoprobes for the noninvasive imaging of angiogenesis , 2009, Proceedings of the National Academy of Sciences.

[159]  Kyung-Han Lee,et al.  Catabolism of 64Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model , 2016, Amino Acids.

[160]  Sumaira Ashraf,et al.  In vivo degeneration and the fate of inorganic nanoparticles. , 2016, Chemical Society reviews.

[161]  R. Haag,et al.  Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation , 2010, Proceedings of the National Academy of Sciences.

[162]  M. Batista,et al.  Radiochemical and biological evaluation of novel 153Sm/166Ho-amino acid-chitosan complexes , 2009 .

[163]  Jianlin Shi,et al.  Silica coated upconversion nanoparticles: a versatile platform for the development of efficient theranostics. , 2015, Accounts of chemical research.

[164]  M. Alonso,et al.  Biodistribution and lymph node retention of polysaccharide-based immunostimulating nanocapsules. , 2014, Vaccine.

[165]  Sanyog Jain,et al.  Synthesis, pharmacoscintigraphic evaluation and antitumor efficacy of methotrexate-loaded, folate-conjugated, stealth albumin nanoparticles. , 2011, Nanomedicine.

[166]  A. Nissan,et al.  Prevention of tumor recurrence and distant metastasis formation in a breast cancer mouse model by biodegradable implant of 131I-norcholesterol. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[167]  Gaurav Sahay,et al.  Endocytosis of nanomedicines. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[168]  H. Maeda The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. , 2001, Advances in enzyme regulation.

[169]  Jean-Christophe Leroux,et al.  Effect of poly(N-vinyl-pyrrolidone)-block-poly(D,L-lactide) as coating agent on the opsonization, phagocytosis, and pharmacokinetics of biodegradable nanoparticles. , 2009, Biomacromolecules.

[170]  Ho-Chun Song,et al.  Lymphatic delivery of 99mTc-labeled dextran acetate particles including cyclosporine A. , 2008, Journal of microbiology and biotechnology.

[171]  J. Hsieh,et al.  Dendrimer nanoscaffolds for potential theranostics of prostate cancer with a focus on radiochemistry. , 2013, Molecular pharmaceutics.

[172]  M. Lee,et al.  Radioisotope carrying polyethylene oxide-polycaprolactone copolymer micelles for targetable bone imaging. , 2002, Biomaterials.

[173]  J. Bading,et al.  Biodistribution and tumor imaging of an anti-CEA single-chain antibody-albumin fusion protein. , 2008, Nuclear medicine and biology.

[174]  G. Lamanna,et al.  Dendrimers in nuclear medical imaging , 2012 .

[175]  J. Steinbach,et al.  Synthesis and biodistribution studies of (3)H- and (64)Cu-labeled dendritic polyglycerol and dendritic polyglycerol sulfate. , 2015, Bioconjugate chemistry.

[176]  A. Fernández-Medarde,et al.  Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[177]  S. Armes,et al.  Non-Fouling Character of Poly[2-(methacryloyloxy)ethyl Phosphorylcholine]-Modified Gold Surfaces Fabricated by the 'Grafting to' Method: Comparison of its Protein Resistance with Poly(ethylene glycol)-Modified Gold Surfaces. , 2009, Macromolecular rapid communications.

[178]  Arne Skretting,et al.  Localized internal radiotherapy with 90Y particles embedded in a new thermosetting alginate gel: A feasibility study in pigs , 2006, Nuclear medicine communications.

[179]  N. G. da Silva,et al.  Size and specificity of radiopharmaceuticals for sentinel lymph node detection , 2011, Acta radiologica.

[180]  Bernd J Pichler,et al.  A Population-Based Gaussian Mixture Model Incorporating 18F-FDG PET and Diffusion-Weighted MRI Quantifies Tumor Tissue Classes , 2016, The Journal of Nuclear Medicine.

[181]  Hamidreza Ghandehari,et al.  Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer-90Y conjugates in treatment of prostate tumors. , 2014, Nuclear medicine and biology.

[182]  H. Ringsdorf,et al.  Polymeric Antitumor Agents on a Molecular and on a Cellular Level , 1981 .

[183]  Samir Mitragotri,et al.  Role of target geometry in phagocytosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[184]  H. Chung,et al.  Nanomaterials for cancer therapy and imaging , 2011, Molecules and cells.

[185]  H. Wu,et al.  The effect of paclitaxel‐loaded nanoparticles with radiation on hypoxic MCF‐7 cells , 2007, Journal of clinical pharmacy and therapeutics.

[186]  T. Lodge,et al.  Thermoresponsive Polymers for Nuclear Medicine: Which Polymer Is the Best? , 2016, Langmuir : the ACS journal of surfaces and colloids.

[187]  Y. Momose,et al.  Biodistribution and kinetics of holmium-166-chitosan complex (DW-166HC) in rats and mice. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[188]  G. Gasser,et al.  New insights into the pretargeting approach to image and treat tumours. , 2016, Chemical Society reviews.

[189]  K. Peter,et al.  A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry. , 2015, Angewandte Chemie.

[190]  Heather M. Hennkens,et al.  Radiometals for combined imaging and therapy. , 2013, Chemical reviews.

[191]  C. Allen,et al.  Block copolymer micelles for delivery of cancer therapy: transport at the whole body, tissue and cellular levels. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[192]  Jörg Huwyler,et al.  Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[193]  Tristan Barrett,et al.  Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging. , 2007, ACS nano.

[194]  Jason S. Lewis,et al.  Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO) , 2014, Journal of medicinal chemistry.

[195]  M. Janier,et al.  Radiolabeled dendritic probes as tools for high in vivo tumor targeting: application to melanoma. , 2015, Journal of materials chemistry. B.

[196]  J. Kučka,et al.  Multistage-targeted pH-responsive polymer conjugate of Auger electron emitter: optimized design and in vivo activity. , 2014, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[197]  R. Reilly,et al.  Multifunctional block copolymer micelles for the delivery of 111In to EGFR-positive breast cancer cells for targeted Auger electron radiotherapy. , 2009, Molecular pharmaceutics.

[198]  J. Zubieta,et al.  Technetium and gallium derived radiopharmaceuticals: comparing and contrasting the chemistry of two important radiometals for the molecular imaging era. , 2010, Chemical reviews.

[199]  Christoph Meyer,et al.  Selective Coupling of Click Anchors to Proteins via Trypsiligase. , 2016, Bioconjugate chemistry.

[200]  K. Kataoka,et al.  Block copolymer micelles for drug delivery: design, characterization and biological significance. , 2001, Advanced drug delivery reviews.

[201]  U. Schubert,et al.  Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. , 2010, Angewandte Chemie.

[202]  Yong Huang,et al.  Improving the blood clearance time of 125I labeled Dex-g-PMAGGCONHTyr by copolymerization , 2011 .

[203]  I. Navarro-Teulon,et al.  Clinical radioimmunotherapy—the role of radiobiology , 2011, Nature Reviews Clinical Oncology.

[204]  Stavroula Sofou,et al.  Anti–Prostate-Specific Membrane Antigen Liposomes Loaded with 225Ac for Potential Targeted Antivascular α-Particle Therapy of Cancer , 2014, The Journal of Nuclear Medicine.

[205]  Rong Tong,et al.  New Strategies in Cancer Nanomedicine. , 2016, Annual review of pharmacology and toxicology.

[206]  K. Ulbrich,et al.  Ellipticine-aimed polymer-conjugated auger electron emitter: multistage organelle targeting approach. , 2011, Bioconjugate chemistry.

[207]  L. Prodi,et al.  Imaging agents based on lanthanide doped nanoparticles. , 2015, Chemical Society reviews.

[208]  H. Staudinger,et al.  Über Isopren und Kautschuk. 5. Mitteilung. Über die Hydrierung des Kautschuks und über seine Konstitution , 1922 .

[209]  Jun Wang,et al.  Surface Charge Switchable Nanoparticles Based on Zwitterionic Polymer for Enhanced Drug Delivery to Tumor , 2012, Advanced materials.

[210]  Noninvasive imaging of dendrimer-type N-glycan clusters: in vivo dynamics dependence on oligosaccharide structure. , 2010, Angewandte Chemie.

[211]  S. Tanase,et al.  Functional Analysis of Recombinant Human Serum Albumin Domains for Pharmaceutical Applications , 2004, Pharmaceutical Research.

[212]  K. Ulbrich,et al.  Polyoxazoline thermoresponsive micelles as radionuclide delivery systems. , 2010, Macromolecular bioscience.

[213]  Volker Wagner,et al.  The emerging nanomedicine landscape , 2006, Nature Biotechnology.

[214]  J. Lemon,et al.  Synthesis, radiolabeling, and bio-imaging of high-generation polyester dendrimers. , 2009, Journal of the American Chemical Society.

[215]  Juan L. Vivero-Escoto,et al.  Inorganic-Organic Hybrid Nanomaterials for Therapeutic and Diagnostic Imaging Applications , 2011, International journal of molecular sciences.

[216]  K. Peter,et al.  Enzyme-mediated site-specific bioconjugation of metal complexes to proteins: sortase-mediated coupling of copper-64 to a single-chain antibody. , 2014, Angewandte Chemie.

[217]  Benjamin R. Jarrett,et al.  Synthesis of 64Cu-labeled magnetic nanoparticles for multimodal imaging. , 2008, Bioconjugate chemistry.

[218]  Jean M. J. Fréchet,et al.  Dendrimers and other dendritic polymers , 2001 .

[219]  Bryan Hoang,et al.  Noninvasive monitoring of the fate of 111In-labeled block copolymer micelles by high resolution and high sensitivity microSPECT/CT imaging. , 2009, Molecular pharmaceutics.

[220]  M. Brechbiel,et al.  Evaluation of the in vivo biodistribution of indium-111 and yttrium-88 labeled dendrimer-1B4M-DTPA and its conjugation with anti-Tac monoclonal antibody. , 1999, Bioconjugate chemistry.

[221]  Ting Zhao,et al.  Pharmacokinetic analysis of in vivo disposition of heparin-superoxide dismutase. , 2010, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[222]  J. Kučka,et al.  Optimized protocol for the radioiodination of hydrazone-type polymer drug delivery systems. , 2015, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[223]  S. H. Park,et al.  Highly efficient method for 125I-radiolabeling of biomolecules using inverse-electron-demand Diels-Alder reaction. , 2016, Bioorganic & medicinal chemistry.

[224]  F. Patel,et al.  Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. , 1994, International journal of radiation oncology, biology, physics.

[225]  Dennis E Discher,et al.  Minimal " Self " Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles References and Notes , 2022 .

[226]  M. Essler,et al.  Synthesis, biodistribution and excretion of radiolabeled poly(2-alkyl-2-oxazoline)s. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[227]  Christina Graf,et al.  Multivalency as a chemical organization and action principle. , 2012, Angewandte Chemie.

[228]  M. Elsabee,et al.  Water-soluble derivatives of chitosan as a target delivery system of 99mTc to some organs in vivo for nuclear imaging and biodistribution , 2011 .

[229]  H. G. van der Poel,et al.  Comparing the Hybrid Fluorescent–Radioactive Tracer Indocyanine Green–99mTc-Nanocolloid with 99mTc-Nanocolloid for Sentinel Node Identification: A Validation Study Using Lymphoscintigraphy and SPECT/CT , 2012, The Journal of Nuclear Medicine.

[230]  F. Kiessling,et al.  Macromolecular nanotheranostics for multimodal anticancer therapy. , 2011, Nanoscale.

[231]  J. Kozempel,et al.  New binary thermoresponsive polymeric system for local chemoradiotherapy , 2009 .

[232]  C. van Nostrum,et al.  Micelles based on HPMA copolymers. , 2010, Advanced drug delivery reviews.

[233]  V. Préat,et al.  RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis. , 2012, Molecular pharmaceutics.

[234]  Hanno Schieferstein,et al.  Radiolabeling of Nanoparticles and Polymers for PET Imaging , 2014, Pharmaceuticals.

[235]  Eun-Mi Kim,et al.  Dextran-conjugated vascular endothelial growth factor receptor antibody for in vivo melanoma xenografted mouse imaging. , 2012, Cancer biotherapy & radiopharmaceuticals.

[236]  C. Hoh,et al.  Sentinel Lymph Node Mapping of the Colon and Stomach Using Lymphoseek in a Pig Model , 2004, Annals of Surgical Oncology.

[237]  S. Subramanian,et al.  Technetium-99m-labeled poly(DL-lactide-co-glycolide) nanoparticles as an alternative for sentinel lymph node imaging. , 2010, Cancer biotherapy & radiopharmaceuticals.

[238]  A. Maitra,et al.  Labeling efficiency and biodistribution of Technetium-99m labeled nanoparticles: interference by colloidal tin oxide particles. , 2005, International journal of pharmaceutics.

[239]  Luisa De Cola,et al.  Ultrasmall inorganic nanoparticles: State-of-the-art and perspectives for biomedical applications. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[240]  DashAshutosh,et al.  Peptide Receptor Radionuclide Therapy: An Overview , 2015 .

[241]  Nathan C. Gianneschi,et al.  Stimuli-Responsive Nanomaterials for Biomedical Applications , 2014, Journal of the American Chemical Society.

[242]  F. Franconi,et al.  Superparamagnetic Liposomes for MRI Monitoring and External Magnetic Field‐Induced Selective Targeting of Malignant Brain Tumors , 2015 .

[243]  Liangfang Zhang,et al.  Current Advances in Polymer-Based Nanotheranostics for Cancer Treatment and Diagnosis , 2014, ACS applied materials & interfaces.

[244]  M. Schwaiger,et al.  Systemic Image-Guided Liver Cancer Radiovirotherapy Using Dendrimer-Coated Adenovirus Encoding the Sodium Iodide Symporter as Theranostic Gene , 2013, The Journal of Nuclear Medicine.

[245]  M. Mok,et al.  Evaluation of Performance of Measurement of Faecal α1-Antitrypsin Clearance and Technetium-99m Human Serum Albumin Scintigraphy in Protein-Losing Enteropathy , 2011, Digestion.

[246]  Tamer Refaat,et al.  Cancer active targeting by nanoparticles: a comprehensive review of literature , 2015, Journal of Cancer Research and Clinical Oncology.

[247]  Steven M. Larson,et al.  Radioimmunotherapy of human tumours , 2015, Nature Reviews Cancer.

[248]  H. Maeda,et al.  A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next‐Generation Chemotherapeutics and Photodynamic Therapy—Problems, Solutions, and Prospects , 2016, Microcirculation.

[249]  A. Delgado,et al.  Radiolabelled biodegradable microspheres for lung imaging. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[250]  K. Ulbrich,et al.  Effect of physicochemical modification on the biodistribution and tumor accumulation of HPMA copolymers. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[251]  Jiyun Shi,et al.  Synthesis, characterization, and in vivo biodistribution of 125I-labeled Dex-g-PMAGGCONHTyr. , 2011, Biomacromolecules.

[252]  O. Thews,et al.  18F-Radiolabeling, preliminary evaluation of folate-pHPMA conjugates via PET. , 2014, Macromolecular bioscience.

[253]  W. Oyen,et al.  PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[254]  M. Amiji,et al.  Image-guided nanosystems for targeted delivery in cancer therapy. , 2012, Current medicinal chemistry.

[255]  H. Stephan,et al.  Nuclear and optical dual-labelled imaging agents , 2016, Nuklearmedizin.

[256]  J. Nah,et al.  Asialoglycoprotein-receptor-targeted hepatocyte imaging using 99mTc galactosylated chitosan. , 2006, Nuclear medicine and biology.

[257]  Kai Liu,et al.  Rapid size-controlled synthesis of dextran-coated, 64Cu-doped iron oxide nanoparticles. , 2012, ACS nano.

[258]  Hong Wu,et al.  Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro , 2008, Cancer biology & therapy.

[259]  H. Hong,et al.  Theranostic Unimolecular Micelles Based on Brush-Shaped Amphiphilic Block Copolymers for Tumor-Targeted Drug Delivery and Positron Emission Tomography Imaging , 2014, ACS applied materials & interfaces.

[260]  P. Bartenstein,et al.  A Universally Applicable 68Ga-Labeling Technique for Proteins , 2011, The Journal of Nuclear Medicine.

[261]  Eric Pridgen,et al.  Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles , 2008, Molecular pharmaceutics.

[262]  Changren Zhou,et al.  Polysaccharides-based nanoparticles as drug delivery systems. , 2008, Advanced drug delivery reviews.

[263]  Y. Ikada,et al.  Body distribution of intravenously administered gelatin with different molecular weights , 1994 .

[264]  E. Blomquist,et al.  Cellular retention of radioactivity and increased radiation dose. Model experiments with EGF-dextran. , 2003, Nuclear medicine and biology.

[265]  R. Haag,et al.  Dendritic nanocarriers based on hyperbranched polymers. , 2015, Chemical Society reviews.

[266]  H. Ringsdorf Hermann Staudinger and the future of polymer research jubilees-beloved occasions for cultural piety. , 2004, Angewandte Chemie.

[267]  Leone Spiccia,et al.  Nanomaterials: Applications in Cancer Imaging and Therapy , 2011, Advanced materials.

[268]  Min Li,et al.  Synthesis, metal chelate stability studies, and enzyme digestion of a peptide-linked DOTA derivative and its corresponding radiolabeled immunoconjugates. , 1993, Bioconjugate chemistry.

[269]  Daisuke Ishii,et al.  gamma-Glutamyl PAMAM dendrimer as versatile precursor for dendrimer-based targeting devices. , 2010, Bioconjugate chemistry.

[270]  D. Needham,et al.  Novel radioisotope-based nanomedical approaches , 2013 .

[271]  L. Spiccia,et al.  Synthesis, Copper(II) Complexation, (64)Cu-Labeling, and Bioconjugation of a New Bis(2-pyridylmethyl) Derivative of 1,4,7-Triazacyclononane. , 2008, Bioconjugate chemistry.

[272]  Xiaoping Xu,et al.  Synthesis, biodistribution, and microsingle photon emission computed tomography (SPECT) imaging study of technetium-99m labeled PEGylated dendrimer poly(amidoamine) (PAMAM)-folic acid conjugates. , 2010, Journal of medicinal chemistry.

[273]  Harpreet Kaur,et al.  Synthesis and Characterization of Theranostic Poly(HPMA)-c(RGDyK)-DOTA-64Cu Copolymer Targeting Tumor Angiogenesis: Tumor Localization Visualized by Positron Emission Tomography , 2013, Molecular imaging.

[274]  Richard Hoogenboom,et al.  Click chemistry beyond metal-catalyzed cycloaddition. , 2009, Angewandte Chemie.

[275]  R. Mehvar Dextrans for targeted and sustained delivery of therapeutic and imaging agents. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[276]  Ick Chan Kwon,et al.  Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin: in vivo biodistribution and anti-tumor activity. , 2006, Biomaterials.

[277]  Kyung-Han Lee,et al.  Tumor-homing glycol chitosan-based optical/PET dual imaging nanoprobe for cancer diagnosis. , 2014, Bioconjugate chemistry.

[278]  Ick Chan Kwon,et al.  Facile method to radiolabel glycol chitosan nanoparticles with (64)Cu via copper-free click chemistry for MicroPET imaging. , 2013, Molecular pharmaceutics.

[279]  A. Villringer,et al.  The Use of Radiolabelled Human Serum Albumin and SPECT/MRI Co-Registration to Study Inflammation in The Cavernous Sinus of Cluster Headache Patients , 2006, Cephalalgia : an international journal of headache.

[280]  Andrea Protti,et al.  (⁹⁹m)Tc-bisphosphonate-iron oxide nanoparticle conjugates for dual-modality biomedical imaging. , 2011, Bioconjugate chemistry.

[281]  Yiyun Cheng,et al.  Stimuli-responsive dendrimers in drug delivery. , 2016, Biomaterials science.

[282]  Katayoun Saatchi,et al.  Long-circulating non-toxic blood pool imaging agent based on hyperbranched polyglycerols. , 2012, International journal of pharmaceutics.

[283]  Liangping Zhou,et al.  Single Ho3+‐Doped Upconversion Nanoparticles for High‐Performance T2‐Weighted Brain Tumor Diagnosis and MR/UCL/CT Multimodal Imaging , 2014 .

[284]  Jens Pietzsch,et al.  Yttrium-86-labelled human serum albumin microspheres: relation of surface structure with in vivo stability. , 2008, Nuclear medicine and biology.

[285]  Lingzhou Zhao,et al.  Radionuclide (131)I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors. , 2015, Nanoscale.

[286]  W. Oyen,et al.  Reducing Renal Uptake of Radiolabeled Peptides Using Albumin Fragments , 2008, Journal of Nuclear Medicine.

[287]  R. Counsell,et al.  Radioiodination techniques for small organic molecules , 1982 .

[288]  R. Vile,et al.  Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[289]  Xiaoyang Xu,et al.  Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. , 2014, Advanced drug delivery reviews.

[290]  Y. Sugiyama,et al.  Long-circulating poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles with modulated surface charge. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[291]  Ronnie H. Fang,et al.  Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform , 2011, Proceedings of the National Academy of Sciences.

[292]  Wang Yongxian,et al.  Preparation and radiolabeling of human serum albumin (HSA)-coated magnetite nanoparticles for magnetically targeted therapy. , 2004, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[293]  Christine Allen,et al.  The effects of particle size and molecular targeting on the intratumoral and subcellular distribution of polymeric nanoparticles. , 2010, Molecular pharmaceutics.

[294]  A. Wallace,et al.  The efficacy of Tilmanocept in sentinel lymph mode mapping and identification in breast cancer patients: a comparative review and meta-analysis of the 99mTc-labeled nanocolloid human serum albumin standard of care , 2012, Clinical & Experimental Metastasis.

[295]  Ronnie H. Fang,et al.  Polymeric nanotherapeutics: clinical development and advances in stealth functionalization strategies. , 2014, Nanoscale.

[296]  Ralph Weissleder,et al.  Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis , 2008, Circulation.

[297]  Y. Magata,et al.  Radiolabeled γ-polyglutamic acid complex as a nano-platform for sentinel lymph node imaging. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[298]  Jonathan R. McDaniel,et al.  Brachytherapy using injectable seeds that are self-assembled from genetically encoded polypeptides in situ. , 2012, Cancer research.

[299]  H. Kessler,et al.  Radiolabelled RGD peptides for imaging and therapy , 2012, European Journal of Nuclear Medicine and Molecular Imaging.

[300]  David J. Yang,et al.  99m Tc-glycopeptide: synthesis, biodistribution and imaging in breast tumor-bearing rodents. , 2008, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[301]  Hong Wu,et al.  Cellular uptake and radiosensitization of SR-2508 loaded PLGA nanoparticles , 2008 .

[302]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[303]  Michael V. Green,et al.  Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging. , 2015, Nuclear Medicine and Biology.

[304]  H. Maeda,et al.  Exploiting the enhanced permeability and retention effect for tumor targeting. , 2006, Drug discovery today.

[305]  Y. Magata,et al.  Optimization of dendrimer structure for sentinel lymph node imaging: Effects of generation and terminal group. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[306]  C. Mamat,et al.  Recent Trends in Bioorthogonal Click-Radiolabeling Reactions Using Fluorine-18 , 2013, Molecules.

[307]  C. Hoh,et al.  Minimally invasive sentinel lymph node mapping of the pig colon with Lymphoseek. , 2006, Surgery.

[308]  J. Forman,et al.  Prostate brachytherapy. An overview , 1993, Cancer.

[309]  R. Duncan The dawning era of polymer therapeutics , 2003, Nature Reviews Drug Discovery.

[310]  S. Kapoor,et al.  Detecting protein losing enteropathy by Tc-99m dextran scintigraphy: A novel experience , 2002, Indian journal of pediatrics.

[311]  K. Togashi,et al.  Radionuclide therapy using nanoparticle of 131I-Lactosome in combination with percutaneous ethanol injection therapy , 2013, Journal of Nanoparticle Research.

[312]  H. Morawetz Difficulties in the Emergence of the Polymer Concept—an Essay , 1987 .

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

[314]  T. Wheldon,et al.  Targeted radiotherapy using Auger electron emitters. , 1996, Physics in medicine and biology.

[315]  Lisa Brannon-Peppas,et al.  Active targeting schemes for nanoparticle systems in cancer therapeutics. , 2008, Advanced drug delivery reviews.

[316]  D. Tomalia,et al.  Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging. , 2007, Biochemical Society transactions.

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

[318]  H. Ghandehari,et al.  Nanocarriers for nuclear imaging and radiotherapy of cancer. , 2006, Current pharmaceutical design.

[319]  G. Viljoen,et al.  The role of nuclear technologies in the diagnosis and control of livestock diseases—a review , 2012, Tropical Animal Health and Production.

[320]  Marina V Backer,et al.  Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes , 2007, Nature Medicine.

[321]  W. Hennink,et al.  Characterization of holmium loaded alginate microspheres for multimodality imaging and therapeutic applications. , 2007, Journal of biomedical materials research. Part A.

[322]  Samuel Achilefu,et al.  Introduction to concepts and strategies for molecular imaging. , 2010, Chemical reviews.

[323]  G. V. van Dongen,et al.  Nanobodies Targeting the Hepatocyte Growth Factor: Potential New Drugs for Molecular Cancer Therapy , 2012, Molecular Cancer Therapeutics.

[324]  Hong Ding,et al.  Image Guided Biodistribution and Pharmacokinetic Studies of Theranostics , 2012, Theranostics.

[325]  K. Ocakoglu,et al.  Synthesis and biological evaluation of radiolabeled photosensitizer linked bovine serum albumin nanoparticles as a tumor imaging agent. , 2012, International journal of pharmaceutics.

[326]  J. Kučka,et al.  Thermoresponsive polymeric radionuclide delivery system--an injectable brachytherapy. , 2011, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[327]  Li Tang,et al.  Smart chemistry in polymeric nanomedicine. , 2014, Chemical Society reviews.

[328]  Kevin Braeckmans,et al.  Cell uptake, cytoplasmic diffusion and nuclear access of a 6.5 nm diameter dendrimer. , 2007, International journal of pharmaceutics.

[329]  Xiaodi Zhang,et al.  Microenvironment-Driven Bioelimination of Magnetoplasmonic Nanoassemblies and Their Multimodal Imaging-Guided Tumor Photothermal Therapy. , 2016, ACS nano.

[330]  I. Hajdú,et al.  Folate receptor targeted self-assembled chitosan-based nanoparticles for SPECT/CT imaging: demonstrating a preclinical proof of concept. , 2014, International journal of pharmaceutics.

[331]  Fredrik Y Frejd,et al.  Site-Specific Radiometal Labeling and Improved Biodistribution Using ABY-027, A Novel HER2-Targeting Affibody Molecule–Albumin-Binding Domain Fusion Protein , 2013, The Journal of Nuclear Medicine.

[332]  F. Švec,et al.  Silver-coated monolithic columns for separation in radiopharmaceutical applications. , 2014, Journal of separation science.

[333]  K. Ulbrich,et al.  POLY(HPMA)-COATED LIPOSOMES DEMONSTRATE PROLONGED CIRCULATION IN MICE , 2001, Journal of liposome research.

[334]  Kit S Lam,et al.  Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer , 2012, International journal of nanomedicine.

[335]  J. R. Wolf Review: radiolabeled polymers containing covalently bound (3) H and (14) C. , 2016, Journal of labelled compounds & radiopharmaceuticals.

[336]  Martin W. Brechbiel,et al.  Metal-chelate-dendrimer-antibody constructs for use in radioimmunotherapy and imaging , 1994 .

[337]  H. Staudinger,et al.  Über die Darstellung von Isopren aus Terpenkohlenwasserstoffen , 1911 .

[338]  P. Conti,et al.  Radiopharmaceutical chemistry for positron emission tomography. , 2010, Advanced drug delivery reviews.

[339]  T. Zhao,et al.  Bioapplications of hyperbranched polymers. , 2015, Chemical Society reviews.

[340]  Gert Storm,et al.  Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system , 1995 .

[341]  H. Maeda,et al.  Development of next-generation macromolecular drugs based on the EPR effect: challenges and pitfalls , 2015, Expert opinion on drug delivery.

[342]  J. Kopeček,et al.  Effect of molecular weight (Mw) of N-(2-hydroxypropyl)methacrylamide copolymers on body distribution and rate of excretion after subcutaneous, intraperitoneal, and intravenous administration to rats. , 1987, Journal of biomedical materials research.

[343]  F. Wuest,et al.  18F-Labeled Peptides: The Future Is Bright , 2014, Molecules.

[344]  Pharmacokinetic considerations for targeted drug delivery. , 2013, Advanced drug delivery reviews.

[345]  P. Choyke,et al.  Improved micro-distribution of antibody-photon absorber conjugates after initial near infrared photoimmunotherapy (NIR-PIT). , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[346]  Jiajing Zhang,et al.  Synthesis of poly(ethylene glycol)-b-poly(N-(2-hydroxypropyl) methacrylamide) block copolymers with well-defined structures and their influence on in vivo circulation and biodistribution , 2014 .

[347]  Michael J Welch,et al.  Nanoparticles labeled with positron emitting nuclides: advantages, methods, and applications. , 2012, Bioconjugate chemistry.

[348]  Hao Hong,et al.  Positron Emission Tomography Image-Guided Drug Delivery: Current Status and Future Perspectives , 2014, Molecular pharmaceutics.

[349]  Hao Wang,et al.  RETRACTED ARTICLE: Cu2ZnSnSe4 quantum dots with controllable size and quantum confinement effect , 2013, Journal of Nanoparticle Research.

[350]  C. Vanhove,et al.  Sortase A-mediated site-specific labeling of camelid single-domain antibody-fragments: a versatile strategy for multiple molecular imaging modalities. , 2016, Contrast media & molecular imaging.

[351]  I. Hajdú,et al.  (99m)Tc-labelled nanosystem as tumour imaging agent for SPECT and SPECT/CT modalities. , 2013, International journal of pharmaceutics.

[352]  B. Line,et al.  Clinical production of pharmaceutical grade Tc-99m dextran 70 for lymphoscintigraphy. , 2000, Clinical nuclear medicine.

[353]  Erkki Ruoslahti,et al.  Peptides as Targeting Elements and Tissue Penetration Devices for Nanoparticles , 2012, Advanced materials.

[354]  A. Thompson,et al.  Development of 18F-fluorinatable dendrons and their application to cancer cell targeting , 2011 .

[355]  A. Corti,et al.  How to improve exposure of tumor cells to drugs: promoter drugs increase tumor uptake and penetration of effector drugs. , 2012, Advanced drug delivery reviews.

[356]  C. Hoh,et al.  Preclinical studies of [(99m)Tc]DTPA-mannosyl-dextran . , 2003, Nuclear medicine and biology.

[357]  Yuko Nakamura,et al.  Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer? , 2016, Bioconjugate chemistry.

[358]  Chang-Moon Lee,et al.  Peptide-loaded nanoparticles and radionuclide imaging for individualized treatment of myocardial ischemia. , 2014, Radiology.

[359]  R. Elashoff,et al.  Minimally invasive breast carcinoma staging using lymphatic mapping with radiolabeled dextran , 1998, Cancer.

[360]  M. Sadeghi,et al.  Preparation and characterization of chitosan-capped radioactive gold nanoparticles: neutron irradiation impact on structural properties , 2016, Journal of the Iranian Chemical Society.

[361]  M. Brechbiel,et al.  Rational design, synthesis, and evaluation of tetrahydroxamic acid chelators for stable complexation of zirconium(IV). , 2014, Chemistry.

[362]  J. Li,et al.  Targeted Delivery of Superoxide Dismutase by Chemical Modification with Quaternary Ammonium Chitosan and Pharmacokinetic Analysis , 2015, Journal of Pharmaceutical Innovation.

[363]  Sonja Loges,et al.  Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. , 2013, The Journal of clinical investigation.

[364]  M. Elsabee,et al.  Lactosaminated N-succinyl-chitosan as a liver-targeted carrier of 99mTc in vivo for nuclear imaging and biodistribution , 2011 .

[365]  Matthew Bogyo,et al.  Design of Protease Activated Optical Contrast Agents That Exploit a Latent Lysosomotropic Effect for Use in Fluorescence-Guided Surgery , 2015, ACS chemical biology.

[366]  Ruth Duncan,et al.  Polymer conjugates as anticancer nanomedicines , 2006, Nature Reviews Cancer.

[367]  M J Welch,et al.  Copper-64-labeled antibodies for PET imaging. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[368]  C. Hoh,et al.  Lymphoseek: A Molecular Imaging Agent for Melanoma Sentinel Lymph Node Mapping , 2007, Annals of Surgical Oncology.

[369]  Shiyu Feng,et al.  Radiolabeling of folic acid-modified chitosan with (99m)Tc as potential agents for folate-receptor-mediated targeting. , 2011, Bioorganic & medicinal chemistry letters.

[370]  J. Correia,et al.  Mannosylated dextran derivatives labeled with fac-[M(CO)₃]+ (M = (99m)Tc, Re) for specific targeting of sentinel lymph node. , 2011, Molecular pharmaceutics.

[371]  Weibo Cai,et al.  Dual-Modality Positron Emission Tomography/Optical Image-Guided Photodynamic Cancer Therapy with Chlorin e6-Containing Nanomicelles. , 2016, ACS nano.

[372]  D. Yan,et al.  188Re-labeled hyperbranched polysulfonamine as a robust tool for targeted cancer diagnosis and radioimmunotherapy , 2013, Chinese Journal of Polymer Science.

[373]  N. G. da Silva,et al.  Parameters optimization defined by statistical analysis for cysteine-dextran radiolabeling with technetium tricarbonyl core. , 2011, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[374]  Adrian House,et al.  PET Imaging and Biodistribution of Silicon Quantum Dots in Mice. , 2011, ACS medicinal chemistry letters.

[375]  W. Oyen,et al.  αvβ3 Integrin‐targeting of intraperitoneally growing tumors with a radiolabeled RGD peptide , 2007 .

[376]  Hwan-Jeong Jeong,et al.  Radiolabeled chitosan hydrogel containing VEGF enhances angiogenesis in a rodent model of acute myocardial infarction , 2014, Macromolecular Research.

[377]  K. Ulbrich,et al.  New bioerodable thermoresponsive polymers for possible radiotherapeutic applications. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[378]  D. Hellwig,et al.  Positronenemissionstomographie 2013 in Deutschland , 2015, Nuklearmedizin.

[379]  I. Broer,et al.  Tailoring plant metabolism for the production of novel polymers and platform chemicals. , 2010, Current opinion in plant biology.

[380]  Yonggang Wei,et al.  In vivo distribution of (131)I and (125)I dual-labeled gelatin microspheres after implantation into rabbit liver. , 2012, Cancer biotherapy & radiopharmaceuticals.

[381]  Leone Spiccia,et al.  Zwitterionic-coated "stealth" nanoparticles for biomedical applications: recent advances in countering biomolecular corona formation and uptake by the mononuclear phagocyte system. , 2014, Small.

[382]  Hsin-Ell Wang,et al.  Cancer nanotargeted radiopharmaceuticals for tumor imaging and therapy. , 2009, Anticancer research.

[383]  L. Feinendegen,et al.  Development of DNA-based radiopharmaceuticals carrying Auger-electron emitters for anti-gene radiotherapy. , 2000, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[384]  Mansoor Amiji,et al.  Biodistribution and Targeting Potential of Poly(ethylene glycol)-modified Gelatin Nanoparticles in Subcutaneous Murine Tumor Model , 2004, Journal of drug targeting.