New radiotracers for imaging of vascular targets in angiogenesis-related diseases.

Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients.

[1]  Weibo Cai,et al.  Imaging of integrins as biomarkers for tumor angiogenesis. , 2008, Current pharmaceutical design.

[2]  Hao Hong,et al.  Preparation and functionalization of graphene nanocomposites for biomedical applications , 2013, Nature Protocols.

[3]  Kai Yang,et al.  Tumor vasculature targeting and imaging in living mice with reduced graphene oxide. , 2013, Biomaterials.

[4]  S. Jalkanen,et al.  Cloning of  Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule , 1998, The Journal of experimental medicine.

[5]  L. Dinkelborg,et al.  Imaging of tumor angiogenesis using 99mTc-labeled human recombinant anti-ED-B fibronectin antibody fragments. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  Rebecca E. Sohn,et al.  Detection of Rapalog-Mediated Therapeutic Response in Renal Cancer Xenografts Using 64Cu-bevacizumab ImmunoPET , 2013, PloS one.

[7]  Anna M Wu,et al.  Antibodies for Molecular Imaging of Cancer , 2008, Cancer journal.

[8]  Carolyn J. Anderson,et al.  Correction: Very Late Antigen-4 (α4β1 Integrin) Targeted PET Imaging of Multiple Myeloma , 2013, PLoS ONE.

[9]  A. Koch,et al.  Angiogenesis and vasculogenesis in rheumatoid arthritis , 2010, Current opinion in rheumatology.

[10]  Yin Zhang,et al.  Positron Emission Tomography Imaging of CD105 Expression with a 64Cu-Labeled Monoclonal Antibody: NOTA Is Superior to DOTA , 2011, PloS one.

[11]  F. Jamar,et al.  A comparison between 111In-anti-E-selectin mAb and 99Tcm-labelled human non-specific immunoglobulin in radionuclide imaging of rheumatoid arthritis. , 1997, The British journal of radiology.

[12]  W. Fang,et al.  A potential thrombus diagnosis reagent based on P-selectin monoclonal antibody SZ-51 light chain. , 2008, Thrombosis research.

[13]  Yin Zhang,et al.  PET/SPECT imaging of hindlimb ischemia: focusing on angiogenesis and blood flow , 2012, Angiogenesis.

[14]  Xiaoyuan Chen,et al.  Imaging tumor endothelial marker 8 using an 18F-labeled peptide , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  J. Kriegsmann,et al.  Expression of E-selectin messenger RNA and protein in rheumatoid arthritis. , 1995, Arthritis and rheumatism.

[16]  Napoleone Ferrara,et al.  Vascular endothelial growth factor: basic science and clinical progress. , 2004, Endocrine reviews.

[17]  J. Alsac,et al.  Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation , 2011, The Journal of Nuclear Medicine.

[18]  S. Jalkanen,et al.  The oxidase activity of vascular adhesion protein-1 (VAP-1) induces endothelial E- and P-selectins and leukocyte binding. , 2007, Blood.

[19]  Sanjiv S Gambhir,et al.  Monitoring of the Biological Response to Murine Hindlimb Ischemia With 64Cu-Labeled Vascular Endothelial Growth Factor-121 Positron Emission Tomography , 2008, Circulation.

[20]  Jelena Mandic,et al.  Chemomechanical mapping of ligand–receptor binding kinetics on cells , 2007, Proceedings of the National Academy of Sciences.

[21]  M. Sans,et al.  VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis. , 1999, Gastroenterology.

[22]  S. Kaul,et al.  Molecular Imaging of Endothelial Vascular Cell Adhesion Molecule-1 Expression and Inflammatory Cell Recruitment During Vasculogenesis and Ischemia-Mediated Arteriogenesis , 2008, Circulation.

[23]  Xiaoming Wang,et al.  Chapter 7 , 2003, School Health Policy & Practice.

[24]  R. Sarkar,et al.  Matrix metalloproteinases in vascular physiology and disease , 2012, Vascular.

[25]  K. Lam,et al.  111In-LLP2A-DOTA Polyethylene Glycol–Targeting α4β1 Integrin: Comparative Pharmacokinetics for Imaging and Therapy of Lymphoid Malignancies , 2009, Journal of Nuclear Medicine.

[26]  岸本 浩史 Obstructive jaundice facilitates hepatic metastasis of B16F1 mouse melanoma cells : participation of increased VCAM-1 expression in the liver , 2002 .

[27]  R. Liddington,et al.  Selection of Anthrax Toxin Protective Antigen Variants That Discriminate between the Cellular Receptors TEM8 and CMG2 and Achieve Targeting of Tumor Cells* , 2007, Journal of Biological Chemistry.

[28]  J. Folkman Opinion: Angiogenesis: an organizing principle for drug discovery? , 2007, Nature Reviews Drug Discovery.

[29]  Donald Gullberg,et al.  Integrins , 2009, Cell and Tissue Research.

[30]  Kai Chen,et al.  Positron Emission Tomography Imaging of Poststroke Angiogenesis , 2009, Stroke.

[31]  D. Boturyn,et al.  Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[32]  T. Byzova,et al.  Inflammation and oxidative stress in angiogenesis and vascular disease , 2013, Journal of Molecular Medicine.

[33]  E. Pasquale,et al.  Eph receptor signaling and ephrins. , 2013, Cold Spring Harbor perspectives in biology.

[34]  P. Circosta,et al.  Ab-induced ectodomain shedding mediates hepatocyte growth factor receptor down-regulation and hampers biological activity. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[35]  L. Cryan,et al.  Targeting the anthrax receptors, TEM-8 and CMG-2, for anti-angiogenic therapy. , 2011, Frontiers in bioscience.

[36]  L. Ehret-Sabatier,et al.  Synthesis of an activated phosphonated bifunctional chelate with potential for PET imaging and radiotherapy. , 2012, Organic & biomolecular chemistry.

[37]  Junho Chung,et al.  Characterization, biodistribution and small-animal SPECT of I-125-labeled c-Met binding peptide in mice bearing c-Met receptor tyrosine kinase-positive tumor xenografts. , 2009, Nuclear medicine and biology.

[38]  M. Cybulsky,et al.  Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. , 1999, Circulation research.

[39]  M. Knopp,et al.  Pharmacokinetic Properties of Intravitreal I-124-Aflibercept in a Rabbit Model Using PET/CT , 2012, Current eye research.

[40]  G. V. van Dongen,et al.  Facile labelling of an anti-epidermal growth factor receptor Nanobody with 68Ga via a novel bifunctional desferal chelate for immuno-PET , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[41]  D. Bottaro,et al.  Targeting the c-Met signaling pathway in cancer. , 2008, Clinical cancer research : an official journal of the American Association for Cancer Research.

[42]  P. Chapman,et al.  Imaging vascular endothelial activation: an approach using radiolabeled monoclonal antibodies against the endothelial cell adhesion molecule E-selectin. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[43]  Xiaoyuan Chen,et al.  Positron emission tomography imaging of cancer biology: current status and future prospects. , 2011, Seminars in oncology.

[44]  Xiyun Yan,et al.  CD146, a multi-functional molecule beyond adhesion. , 2013, Cancer letters.

[45]  Marc C. Huisman,et al.  Phase 0 Microdosing PET Study Using the Human Mini Antibody F16SIP in Head and Neck Cancer Patients , 2013, The Journal of Nuclear Medicine.

[46]  A. Kutlar,et al.  Cellular adhesion and the endothelium: P-selectin. , 2014, Hematology/oncology clinics of North America.

[47]  B. Seon,et al.  Effective anti-angiogenic therapy of established tumors in mice by naked anti-human endoglin (CD105) antibody: differences in growth rate and therapeutic response between tumors growing at different sites. , 2006, International journal of oncology.

[48]  G Germano,et al.  Dual-isotope myocardial perfusion SPECT with rest thallium-201 and stress Tc-99m sestamibi. , 1994, Cardiology clinics.

[49]  Ma Dong,et al.  Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer , 2006 .

[50]  Hao Hong,et al.  In vivo targeting and positron emission tomography imaging of tumor vasculature with (66)Ga-labeled nano-graphene. , 2012, Biomaterials.

[51]  R. Poston,et al.  Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. , 1994, The American journal of pathology.

[52]  H. Xi,et al.  Eph receptors and ephrins as targets for cancer therapy , 2012, Journal of cellular and molecular medicine.

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

[54]  P. Erba,et al.  Expression of the oncofetal ED-B-containing fibronectin isoform in hematologic tumors enables ED-B-targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients. , 2009, Blood.

[55]  P. Ma,et al.  In vivo positron emission tomography (PET) imaging of mesenchymal-epithelial transition (MET) receptor. , 2010, Journal of medicinal chemistry.

[56]  S. Cannistra,et al.  Vascular cell adhesion molecule-1 expressed by peritoneal mesothelium partly mediates the binding of activated human T lymphocytes. , 1994, Experimental hematology.

[57]  Kai Xu,et al.  Eph/ephrin recognition and the role of Eph/ephrin clusters in signaling initiation. , 2013, Biochimica et biophysica acta.

[58]  Valerie A Longo,et al.  Fluorine-labeled dasatinib nanoformulations as targeted molecular imaging probes in a PDGFB-driven murine glioblastoma model. , 2012, Neoplasia.

[59]  Dong Liang,et al.  Peptide-conjugated polymeric micellar nanoparticles for Dual SPECT and optical imaging of EphB4 receptors in prostate cancer xenografts. , 2011, Biomaterials.

[60]  H. Dauerman,et al.  Increased expression of platelet P-selectin and formation of platelet-leukocyte aggregates in blood from patients treated with unfractionated heparin plus eptifibatide compared with bivalirudin. , 2006, Thrombosis research.

[61]  L. Patterson,et al.  Function and antagonism of beta3 integrins in the development of cancer therapy. , 2009, Current cancer drug targets.

[62]  R. Chiquet‐Ehrismann,et al.  Tenascin-C induced signaling in cancer. , 2006, Cancer letters.

[63]  M. Maio,et al.  Emerging role of endoglin (CD105) as a marker of angiogenesis with clinical potential in human malignancies. , 2003, Current cancer drug targets.

[64]  S. Tanada,et al.  Toward in vivo imaging of heart disease using a radiolabeled single-chain Fv fragment targeting tenascin-C. , 2011, Analytical chemistry.

[65]  Yin Zhang,et al.  Positron emission tomography imaging of CD105 expression in a rat myocardial infarction model with (64)Cu-NOTA-TRC105. , 2013, American journal of nuclear medicine and molecular imaging.

[66]  H. Kosmehl,et al.  Molecular variants of fibronectin and laminin: structure, physiological occurrence and histopathological aspects , 1996, Virchows Archiv.

[67]  Yin Zhang,et al.  Positron emission tomography and optical imaging of tumor CD105 expression with a dual-labeled monoclonal antibody. , 2012, Molecular pharmaceutics.

[68]  Joseph C. Wu,et al.  Noninvasive radionuclide imaging of cardiac gene therapy: progress and potential , 2008, Nature Clinical Practice Cardiovascular Medicine.

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

[70]  Yin Zhang,et al.  Positron emission tomography imaging of CD105 expression during tumor angiogenesis , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[71]  Soonhag Kim,et al.  A multimodal nanoparticle-based cancer imaging probe simultaneously targeting nucleolin, integrin αvβ3 and tenascin-C proteins. , 2011, Biomaterials.

[72]  S. Tanada,et al.  Detection of Experimental Autoimmune Myocarditis in Rats by 111In Monoclonal Antibody Specific for Tenascin-C , 2002, Circulation.

[73]  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.

[74]  Therapeutic angiogenesis for myocardial ischemia revisited: basic biological concepts and focus on latest clinical trials , 2012, Angiogenesis.

[75]  R. Khokha,et al.  Metalloproteinases and their natural inhibitors in inflammation and immunity , 2013, Nature Reviews Immunology.

[76]  Xiaoyuan Chen,et al.  Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. , 2010, Current drug targets.

[77]  J. Zagzebski,et al.  Positron emission tomography imaging of angiogenesis in a murine hindlimb ischemia model with 64Cu-labeled TRC105. , 2013, Molecular pharmaceutics.

[78]  B. Seon,et al.  Antiangiogenic therapy of established tumors in human skin/severe combined immunodeficiency mouse chimeras by anti-endoglin (CD105) monoclonal antibodies, and synergy between anti-endoglin antibody and cyclophosphamide. , 2001, Cancer research.

[79]  W. Oyen,et al.  Imaging liver metastases of colorectal cancer patients with radiolabelled bevacizumab: Lack of correlation with VEGF-A expression. , 2008, European journal of cancer.

[80]  E. Lengyel,et al.  C‐Met overexpression in node‐positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu , 2005, International journal of cancer.

[81]  F. Jamar,et al.  Scintigraphy using a technetium 99m-labelled anti-E-selectin Fab fragment in rheumatoid arthritis. , 2002, Rheumatology.

[82]  U. Haberkorn,et al.  ScVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA conjugates: comparison of easy-to-label recombinant proteins for [68Ga]PET imaging of VEGF receptors in angiogenic vasculature. , 2010, Nuclear medicine and biology.

[83]  Ying-Fon Chang,et al.  Tumor targeting by an aptamer. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[84]  Sanjiv S Gambhir,et al.  A molecular imaging primer: modalities, imaging agents, and applications. , 2012, Physiological reviews.

[85]  G. Niu,et al.  Preclinical molecular imaging of tumor angiogenesis. , 2010, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[86]  R. Soares,et al.  Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox. , 2013, Life sciences.

[87]  Yasuyoshi Watanabe,et al.  Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice. , 2013, Biochemical and biophysical research communications.

[88]  Yin Zhang,et al.  ImmunoPET and near-infrared fluorescence imaging of CD105 expression using a monoclonal antibody dual-labeled with (89)Zr and IRDye 800CW. , 2012, American journal of translational research.

[89]  Yin Zhang,et al.  Positron emission tomography imaging of tumor angiogenesis with a (61/64)Cu-labeled F(ab')(2) antibody fragment. , 2013, Molecular pharmaceutics.

[90]  L. Zardi,et al.  Selective targeting of tumoral vasculature: Comparison of different formats of an antibody (L19) to the ED‐B domain of fibronectin , 2002, International journal of cancer.

[91]  B. Langlois,et al.  Advances in tenascin-C biology , 2011, Cellular and Molecular Life Sciences.

[92]  G. Giaccone,et al.  Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30 , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[93]  E. Hoffman,et al.  Application of annihilation coincidence detection to transaxial reconstruction tomography. , 1975, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[94]  H. Hong,et al.  Pravastatin stimulates angiogenesis in a murine hindlimb ischemia model: a positron emission tomography imaging study with (64)Cu-NOTA-TRC105. , 2013, American journal of translational research.

[95]  A. Cattelan,et al.  Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma. , 1996, British Journal of Cancer.

[96]  Kathrin Kettenbach,et al.  18F-Labeling Using Click Cycloadditions , 2014, BioMed research international.

[97]  C. Anderson,et al.  Comparison of two cross-bridged macrocyclic chelators for the evaluation of 64Cu-labeled-LLP2A, a peptidomimetic ligand targeting VLA-4-positive tumors. , 2013, Nuclear medicine and biology.

[98]  Hao Hong,et al.  PET imaging of CD105/endoglin expression with a 61/64Cu-labeled Fab antibody fragment , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[99]  B. Holzmann,et al.  α4 Integrins and Tumor Metastasis , 1998 .

[100]  M. Gerritsen,et al.  Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse. , 1997, Journal of immunology.

[101]  Hao Hong,et al.  In vivo tumor targeting and image-guided drug delivery with antibody-conjugated, radiolabeled mesoporous silica nanoparticles. , 2013, ACS nano.

[102]  V. Kähäri,et al.  Matrix metalloproteinases in inflammation. , 2014, Biochimica et biophysica acta.

[103]  G. V. van Dongen,et al.  Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models , 2007, British Journal of Cancer.

[104]  B. Cornelissen,et al.  A review of small animal imaging planar and pinhole spect Gamma camera imaging. , 2005, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[105]  G. Minniti,et al.  Integrin inhibitor cilengitide for the treatment of glioblastoma: a brief overview of current clinical results. , 2012, Anticancer research.

[106]  M. Conaway,et al.  Vascular cell adhesion molecule-1 is a regulator of ovarian cancer peritoneal metastasis. , 2009, Cancer research.

[107]  H. Shan,et al.  PET Imaging of Colorectal and Breast Cancer by Targeting EphB4 Receptor with 64Cu-Labeled hAb47 and hAb131 Antibodies , 2013, The Journal of Nuclear Medicine.

[108]  A. Koch,et al.  Angiogenesis and Vasculopathy in Systemic Sclerosis: Evolving Concepts , 2012, Current Rheumatology Reports.

[109]  P. Choyke,et al.  Immuno-PET of the Hepatocyte Growth Factor Receptor Met Using the 1-Armed Antibody Onartuzumab , 2012, The Journal of Nuclear Medicine.

[110]  Martin Lackmann,et al.  Therapeutic targeting of EPH receptors and their ligands , 2013, Nature Reviews Drug Discovery.

[111]  Kai Yang,et al.  The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power. , 2012, Biomaterials.

[112]  D. Neri,et al.  Radioimmunotherapy with Tenarad, a 131I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma , 2014, European Journal of Nuclear Medicine and Molecular Imaging.

[113]  H. Elovaara,et al.  Siglec-9 is a novel leukocyte ligand for vascular adhesion protein-1 and can be used in PET imaging of inflammation and cancer. , 2011, Blood.

[114]  M. Berger,et al.  Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies. , 2006, Neurosurgical focus.

[115]  S. Mather,et al.  A novel model for the pre-clinical imaging of inflamed human synovial vasculature. , 2009, Rheumatology.

[116]  Bo Li,et al.  Fucoidan: Structure and Bioactivity , 2008, Molecules.

[117]  B. Annex,et al.  Therapeutic angiogenesis for critical limb ischaemia , 2013, Nature Reviews Cardiology.

[118]  E. Jubeli,et al.  E-selectin as a target for drug delivery and molecular imaging. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[119]  Yin Zhang,et al.  Multimodality molecular imaging of CD105 (Endoglin) expression. , 2011, International journal of clinical and experimental medicine.

[120]  Kyung-Han Lee,et al.  A vascular endothelial growth factor 121 (VEGF(121))-based dual PET/optical probe for in vivo imaging of VEGF receptor expression. , 2013, Biomaterials.

[121]  Kai Yang,et al.  In vivo targeting and imaging of tumor vasculature with radiolabeled, antibody-conjugated nanographene. , 2012, ACS nano.

[122]  E. Choke,et al.  Potential role for anti‐angiogenic therapy in abdominal aortic aneurysms , 2013, European journal of clinical investigation.

[123]  Weibo Cai,et al.  Multimodality Molecular Imaging of Tumor Angiogenesis , 2008, Journal of Nuclear Medicine.

[124]  M. Westphal,et al.  A Novel One-Armed Anti-c-Met Antibody Inhibits Glioblastoma Growth In vivo , 2006, Clinical Cancer Research.

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

[126]  M. Pepper Role of the Matrix Metalloproteinase and Plasminogen Activator-Plasmin Systems in Angiogenesis , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[127]  R Weissleder,et al.  Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin. , 2000, European journal of cancer.

[128]  W. Fang,et al.  Detection of pulmonary embolism with 99mTc-labeled F(ab)2 fragment of anti-P-selectin monoclonal antibody in dogs. , 2011, The Tohoku journal of experimental medicine.

[129]  K. Alitalo,et al.  Receptor tyrosine kinase-mediated angiogenesis. , 2013, Cold Spring Harbor perspectives in biology.

[130]  P. Jurek,et al.  Conjugation and radiolabeling of monoclonal antibodies with zirconium-89 for PET imaging using the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine , 2010, Nature Protocols.

[131]  S. Jalkanen,et al.  Homing‐associated molecules CD73 and VAP‐1 as targets to prevent harmful inflammations and cancer spread , 2011, FEBS letters.

[132]  S. Jalkanen,et al.  Mini-PEG spacering of VAP-1-targeting 68Ga-DOTAVAP-P1 peptide improves PET imaging of inflammation , 2011, EJNMMI research.

[133]  T. Choueiri,et al.  Targeting the Hepatocyte Growth Factor/c-Met Signaling Pathway in Renal Cell Carcinoma , 2013, Cancer journal.

[134]  A. Sinusas,et al.  Molecular Imaging of Activated Matrix Metalloproteinases in Vascular Remodeling , 2008, Circulation.

[135]  M. Maio,et al.  Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancer , 2004, Journal of Translational Medicine.

[136]  Hao Hong,et al.  Molecular imaging and therapy of cancer with radiolabeled nanoparticles. , 2009, Nano today.

[137]  G. Schultz,et al.  Molecular Wound Assessments: Matrix Metalloproteinases. , 2013, Advances in wound care.

[138]  O. Boerman,et al.  Molecular imaging of angiogenesis with SPECT , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[139]  C. Xiong,et al.  Dual-Modality Micro-Positron Emission Tomography/Computed Tomography and Near-Infrared Fluorescence Imaging of EphB4 in Orthotopic Glioblastoma Xenograft Models , 2014, Molecular Imaging and Biology.

[140]  B. Holzmann,et al.  alpha 4 integrins and tumor metastasis. , 1998, Current topics in microbiology and immunology.

[141]  G. Christofori,et al.  Angiopoietins in angiogenesis. , 2013, Cancer letters.

[142]  Jakub Toczek,et al.  Nanobodies Targeting Mouse/Human VCAM1 for the Nuclear Imaging of Atherosclerotic Lesions , 2012, Circulation research.

[143]  R. Reilly,et al.  111In- or 99mTc-labeled recombinant VEGF bioconjugates: in vitro evaluation of their cytotoxicity on porcine aortic endothelial cells overexpressing Flt-1 receptors. , 2010, Nuclear medicine and biology.

[144]  A. Cribier,et al.  201Tl and 99mTc-MIBI gated SPECT in patients with large perfusion defects and left ventricular dysfunction: comparison with equilibrium radionuclide angiography. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[145]  Robert S. Kerbel,et al.  Antiangiogenic therapy: impact on invasion, disease progression, and metastasis , 2011, Nature Reviews Clinical Oncology.

[146]  Ralph Weissleder,et al.  18F-4V for PET-CT imaging of VCAM-1 expression in atherosclerosis. , 2009, JACC. Cardiovascular imaging.

[147]  L. Ellis,et al.  Endoglin (CD105): A Marker of Tumor Vasculature and Potential Target for Therapy , 2008, Clinical Cancer Research.

[148]  S. Ylä-Herttuala Cardiovascular gene therapy with vascular endothelial growth factors. , 2013, Gene.

[149]  S. Jalkanen,et al.  68Ga-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation in healing bones and the progress of infection in osteomyelitic bones , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[150]  L. Matrisian,et al.  Near-infrared optical proteolytic beacons for in vivo imaging of matrix metalloproteinase activity. , 2010, Methods in molecular biology.

[151]  A. Sinusas,et al.  Radiotracer imaging of peripheral vascular disease. , 2013, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[152]  Dario Neri,et al.  Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[153]  G. Orend Potential oncogenic action of tenascin-C in tumorigenesis. , 2005, The international journal of biochemistry & cell biology.

[154]  H. Hollema,et al.  VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment. , 2011, Cancer research.

[155]  J. Knuuti,et al.  Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis. , 2009, Nuclear medicine and biology.

[156]  P. Perret,et al.  In Vivo Molecular Imaging of Atherosclerotic Lesions in ApoE-/-mice using VCAM-1-Specific , 99 m Tc-Labeled Peptidic Sequences , 2013 .

[157]  Amir Kashefi,et al.  A new PET tracer specific for vascular endothelial growth factor receptor 2 , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[158]  Yihai Cao Multifarious functions of PDGFs and PDGFRs in tumor growth and metastasis. , 2013, Trends in molecular medicine.

[159]  C. Xiong,et al.  In Vivo Small-Animal PET/CT of EphB4 Receptors Using 64Cu-Labeled Peptide , 2011, The Journal of Nuclear Medicine.

[160]  Raquel Soares,et al.  Angiogenesis and chronic inflammation: cause or consequence? , 2007, Angiogenesis.

[161]  S. Jalkanen,et al.  Preliminary evaluation of novel 68Ga‐DOTAVAP‐PEG‐P2 peptide targeting vascular adhesion protein‐1 , 2010, Clinical physiology and functional imaging.

[162]  S. Jalkanen,et al.  Preclinical Evaluation of a Radioiodinated Fully Human Antibody for In Vivo Imaging of Vascular Adhesion Protein-1–Positive Vasculature in Inflammation , 2013, The Journal of Nuclear Medicine.

[163]  M. Sans,et al.  123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis , 2001, European journal of gastroenterology & hepatology.

[164]  P. Wakeley,et al.  Synthesis , 2013, The Role of Animals in Emerging Viral Diseases.

[165]  S. Jalkanen,et al.  Induction and function of vascular adhesion protein-1 at sites of inflammation , 1993, The Journal of experimental medicine.

[166]  N. Ferrara,et al.  VEGF inhibition: insights from preclinical and clinical studies , 2008, Cell and Tissue Research.

[167]  R. Chisin,et al.  Formation of fluorine-18 labeled diaryl ureas--labeled VEGFR-2/PDGFR dual inhibitors as molecular imaging agents for angiogenesis. , 2008, Bioorganic & medicinal chemistry.

[168]  T. Nayak,et al.  PET imaging of tumor angiogenesis in mice with VEGF‐A–targeted 86Y‐CHX‐A″‐DTPA‐bevacizumab , 2011, International journal of cancer.

[169]  Kohei Miyazono,et al.  TGFβ signalling: a complex web in cancer progression , 2010, Nature Reviews Cancer.

[170]  S. Gambhir,et al.  Chapter 7. Molecular imaging of tumor vasculature. , 2008, Methods in enzymology.

[171]  L. Ellis,et al.  Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[172]  S. Pal,et al.  Targeting angiopoietin-2 signaling in cancer therapy , 2013, Expert opinion on investigational drugs.

[173]  M E Phelps,et al.  Effect of positron range on spatial resolution. , 1975, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[174]  S. Tanada,et al.  Noninvasive detection of cardiac repair after acute myocardial infarction in rats by 111 In Fab fragment of monoclonal antibody specific for tenascin-C. , 2008, International heart journal.

[175]  O. Schober,et al.  Molecular imaging of matrix metalloproteinases in vivo using small molecule inhibitors for SPECT and PET. , 2006, Current medicinal chemistry.

[176]  A. Diller,et al.  Technetium-bevacizumab in a patient with bone and lung metastatic colon adenocarcinoma. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[177]  S. Nourshargh,et al.  JAM family and related proteins in leukocyte migration (Vestweber series). , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[178]  Boris Pasche,et al.  TGF-β: duality of function between tumor prevention and carcinogenesis. , 2014, Journal of the National Cancer Institute.

[179]  Xiaoyuan Chen,et al.  Site-Specific Labeling of scVEGF with Fluorine-18 for Positron Emission Tomography Imaging , 2012, Theranostics.

[180]  Carolyn J. Anderson,et al.  Very Late Antigen-4 (α4β1 Integrin) Targeted PET Imaging of Multiple Myeloma , 2013, PloS one.

[181]  J. Folkman Angiogenesis: an organizing principle for drug discovery? , 2007, Nature reviews. Drug discovery.

[182]  S. Dimmeler,et al.  Vascular microRNAs. , 2010, Current drug targets.

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

[184]  M. Welch,et al.  Small-Animal PET of Tumor Angiogenesis Using a 76Br-Labeled Human Recombinant Antibody Fragment to the ED-B Domain of Fibronectin , 2007, Journal of Nuclear Medicine.

[185]  Hua Li,et al.  Comparison of radiation exposure and associated radiation-induced cancer risks from mammography and molecular imaging of the breast. , 2010, Medical physics.

[186]  Mitchel R. Stacy,et al.  Targeted Molecular Imaging of Angiogenesis in PET and SPECT: A Review , 2012, The Yale journal of biology and medicine.

[187]  M. Tabata,et al.  Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using 125I‐labeled anti‐endoglin monoclonal antibodies , 1999, International journal of cancer.

[188]  M. Maio,et al.  Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumours. , 2010, Cardiovascular research.

[189]  Vijay Kumar,et al.  (68)Ga-radiopharmaceuticals for PET imaging of infection and inflammation. , 2013, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[190]  W. Cai,et al.  Quantitative radioimmunoPET imaging of EphA2 in tumor-bearing mice , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[191]  J. Gu,et al.  Construction and Expression of Mouse-human Chimeric Antibody SZ-51 Specific for Activated Platelet P-selectin , 1997, Thrombosis and Haemostasis.

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

[193]  Hao Hong,et al.  Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles. , 2013, Biomaterials.

[194]  A. Pini,et al.  Design and Use of a Phage Display Library , 1998, The Journal of Biological Chemistry.

[195]  R. Jaszczak,et al.  Distribution and dosimetry of I-123-labeled monoclonal antibody 81C6 in patients with anaplastic glioma. , 1993, Investigative radiology.

[196]  Roland Haubner,et al.  Positron emission tomography tracers for imaging angiogenesis , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[197]  S. Jalkanen,et al.  Cell-surface enzymes in control of leukocyte trafficking , 2005, Nature Reviews Immunology.

[198]  A. Berchuck,et al.  Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study. , 2009, Gynecologic oncology.

[199]  G. Karam,et al.  Biochemical and pharmacological characterization of human c-Met neutralizing monoclonal antibody CE-355621 , 2012, mAbs.

[200]  A. Paradiso,et al.  Tumor endothelial markers as a target in cancer , 2012, Expert opinion on therapeutic targets.

[201]  M. Maio,et al.  Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels , 2003, Oncogene.

[202]  W. Oyen,et al.  Tumor accumulation of radiolabeled bevacizumab due to targeting of cell- and matrix-associated VEGF-A isoforms. , 2009, Cancer biotherapy & radiopharmaceuticals.

[203]  William R. Wagner,et al.  Targeted In Vivo Labeling of Receptors for Vascular Endothelial Growth Factor , 2003, Circulation.

[204]  H. Hanaoka,et al.  Positron emission tomography imaging and biodistribution of vascular endothelial growth factor with 64Cu‐labeled bevacizumab in colorectal cancer xenografts , 2011, Cancer science.

[205]  R. Pleijhuis,et al.  89Zr-Bevacizumab PET Imaging in Primary Breast Cancer , 2012, The Journal of Nuclear Medicine.

[206]  A. Menrad,et al.  ED-B fibronectin as a target for antibody-based cancer treatments , 2005, Expert opinion on therapeutic targets.

[207]  A. van Waarde,et al.  Probes for non-invasive matrix metalloproteinase-targeted imaging with PET and SPECT. , 2013, Current pharmaceutical design.

[208]  Yin Zhang,et al.  Positron emission tomography imaging of CD105 expression with 89Zr-Df-TRC105 , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[209]  S. Jalkanen,et al.  PET imaging of inflammation and adenocarcinoma xenografts using vascular adhesion protein 1 targeting peptide 68Ga-DOTAVAP-P1: comparison with 18F-FDG , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[210]  E. Mishani,et al.  Labeled 3-aryl-4-indolylmaleimide derivatives and their potential as angiogenic PET biomarkers. , 2010, Bioorganic & medicinal chemistry.

[211]  F. Segal,et al.  A CHARACTERIZATION OF FIBRANT SEGAL CATEGORIES , 2006, math/0603400.

[212]  S. Perlman,et al.  FDG-PET in inflammatory bowel disease. , 2009, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[213]  J. Chin,et al.  Airway recruitment of leukocytes in mice is dependent on alpha4-integrins and vascular cell adhesion molecule-1. , 1997, The American journal of physiology.

[214]  L. Dinkelborg,et al.  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A High-Affinity Human Antibody That Targets Tumoral Blood Vessels , 1999 .

[215]  M. Daemen,et al.  Novel concepts in atherogenesis: angiogenesis and hypoxia in atherosclerosis , 2009, The Journal of pathology.

[216]  S. Barthel,et al.  Targeting selectins and selectin ligands in inflammation and cancer , 2007, Expert opinion on therapeutic targets.

[217]  N. Ferrara,et al.  Tumor and stromal pathways mediating refractoriness/resistance to anti-angiogenic therapies. , 2009, Trends in pharmacological sciences.

[218]  D. Noonan,et al.  Inflammation, inflammatory cells and angiogenesis: decisions and indecisions , 2008, Cancer and Metastasis Reviews.

[219]  C. Carman Overview: imaging in the study of integrins. , 2012, Methods in molecular biology.

[220]  C. Heldin,et al.  Targeting the PDGF signaling pathway in tumor treatment , 2013, Cell Communication and Signaling.

[221]  L. Claesson‐Welsh,et al.  VEGF receptor signalling ? in control of vascular function , 2006, Nature Reviews Molecular Cell Biology.

[222]  Yin Zhang,et al.  Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW. , 2012, Molecular pharmaceutics.

[223]  J. Berlin,et al.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. , 2004, The New England journal of medicine.

[224]  J. Bowsher,et al.  Dosimetry and radiographic analysis of 131I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[225]  Omid C. Farokhzad,et al.  Current Progress of Aptamer-Based Molecular Imaging , 2014, The Journal of Nuclear Medicine.

[226]  J. K. Kundu,et al.  Emerging avenues linking inflammation and cancer. , 2012, Free radical biology & medicine.

[227]  C. R. Leemans,et al.  124I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of 131I-L19-SIP radioimmunotherapy , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[228]  Philippe Shubik,et al.  VEGF and the quest for tumour angiogenesis factors , 2022 .

[229]  R. Tizard,et al.  Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes , 1989, Cell.

[230]  A. Jemal,et al.  Cancer statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[231]  S. Stone-Elander,et al.  Synthesis and preclinical evaluation of [11C]PAQ as a PET imaging tracer for VEGFR-2 , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[232]  Kyung-Han Lee,et al.  ⁶⁸Ga-NODAGA-VEGF₁₂₁ for in vivo imaging of VEGF receptor expression. , 2014, Nuclear medicine and biology.

[233]  M. Maio,et al.  Endoglin is a suitable target for efficient imaging of solid tumors: in vivo evidence in a canine mammary carcinoma model. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[234]  A. George,et al.  Source of oncofetal ED-B-containing fibronectin: implications of production by both tumor and endothelial cells. , 2000, Cancer research.

[235]  K. Lam,et al.  Molecular Imaging of Very Late Antigen–4 (α4β1 Integrin) in the Premetastatic Niche , 2012, The Journal of Nuclear Medicine.

[236]  L. Zardi,et al.  A tumor-associated fibronectin isoform generated by alternative splicing of messenger RNA precursors , 1989, The Journal of cell biology.

[237]  M. Park,et al.  From Tpr-Met to Met, tumorigenesis and tubes , 2007, Oncogene.

[238]  B. Garmy-Susini,et al.  Integrins in angiogenesis and lymphangiogenesis , 2008, Nature Reviews Cancer.

[239]  R. Coleman,et al.  Dosimetry of 131I-labeled 81C6 monoclonal antibody administered into surgically created resection cavities in patients with malignant brain tumors. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[240]  S. O'dwyer,et al.  Perfusion of 99Tcm‐labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target , 2004, International journal of cancer.

[241]  M. Conaway,et al.  Imaging VCAM-1 as an Indicator of Treatment Efficacy in Metastatic Ovarian Cancer , 2013, The Journal of Nuclear Medicine.

[242]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[243]  Holger Gerhardt,et al.  Basic and Therapeutic Aspects of Angiogenesis , 2011, Cell.

[244]  Yin Zhang,et al.  Positron Emission Tomography and Near-Infrared Fluorescence Imaging of Vascular Endothelial Growth Factor with Dual-Labeled Bevacizumab. , 2012, American journal of nuclear medicine and molecular imaging.

[245]  G. V. van Dam,et al.  Feasibility of Vascular Endothelial Growth Factor Imaging in Human Atherosclerotic Plaque Using 89Zr-Bevacizumab Positron Emission Tomography , 2013, Molecular imaging.

[246]  Kyung Hee Jung,et al.  Progress in cancer therapy targeting c-Met signaling pathway , 2012, Archives of pharmacal research.

[247]  Lei Xu,et al.  Normalization of the vasculature for treatment of cancer and other diseases. , 2011, Physiological reviews.

[248]  David S Mendelson,et al.  A Phase I First-in-Human Study of TRC105 (Anti-Endoglin Antibody) in Patients with Advanced Cancer , 2012, Clinical Cancer Research.

[249]  A. Griffioen,et al.  Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. , 2000, Pharmacological reviews.

[250]  David A Mankoff,et al.  A definition of molecular imaging. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[251]  Eun-Mi Kim,et al.  Iodine 125‐labeled mesenchymal–epithelial transition factor binding peptide‐click‐cRGDyk heterodimer for glioma imaging , 2011, Cancer science.

[252]  Yin Zhang,et al.  Positron emission tomography imaging of vascular endothelial growth factor receptor expression with (61)Cu-labeled lysine-tagged VEGF121. , 2012, Molecular pharmaceutics.