Nuclear medicine applications in molecular imaging

With the emergence of the new field of molecular imaging, there is an increasing demand for development of sensitive and safe novel imaging agents that can be rapidly translated from small animal models into patients. Nuclear medicine and positron emission tomography (PET) techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes, usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at doses free of pharmacologic side effects, unlike the current generation of intravenous agents required for magnetic resonance (MR) and computed tomography (CT) scanning. In this article, we will review a representative sampling of the wide array of radiopharmaceuticals developed specifically for nuclear medicine radionuclide imaging that have been approved for clinical use, and those in pre‐clinical trials. We will also review the existing strategies used to select the appropriate biologic markers and targets for radionuclide labeling that have been employed in the development of novel radiotracers and the imaging of small animals with new microSPECT (single photon emission computed tomography) technologies. J. Magn. Reson. Imaging 2002;16:352–361. © 2002 Wiley‐Liss, Inc.

[1]  E. P. Krenning,et al.  Somatostatin receptor scintigraphy with [111In-DTPA-d-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients , 1993, European Journal of Nuclear Medicine.

[2]  D. Cheresh Structure, function and biological properties of integrin αvβ3on human melanoma cells , 1991, Cancer and Metastasis Reviews.

[3]  Roland Hustinx,et al.  Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[4]  G. Slegers,et al.  Tumour angiogenesis pathways: related clinical issues and implications for nuclear medicine imaging , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[5]  W. Oyen,et al.  Effects of coligand variation on the in vivo characteristics of Tc-99m-labeled interleukin-8 in detection of infection. , 2002, Bioconjugate chemistry.

[6]  M. Hendrix,et al.  Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: Role in vasculogenic mimicry , 2002, The Prostate.

[7]  E. G. Hoffman,et al.  Age-associated changes in methylation of the insulin-like growth factor II (IGF-II) gene , 2002 .

[8]  D. Wong In vivo imaging of D2 dopamine receptors in schizophrenia: the ups and downs of neuroimaging research. , 2002, Archives of general psychiatry.

[9]  J. Booij,et al.  Evaluation of high-resolution pinhole SPECT using a small rotating animal. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  F. Blankenberg,et al.  Annexin-V imaging for noninvasive detection of cardiac allograft rejection , 2001, Nature Medicine.

[11]  P. Slomka,et al.  Subjective Effects of AMPT-induced Dopamine Depletion in Schizophrenia: Correlation between Dysphoric Responses and Striatal D2 Binding Ratios on SPECT Imaging , 2001, Neuropsychopharmacology.

[12]  B. Giraudeau,et al.  Quantitative analysis of striatal dopamine D2 receptors with 123I-iodolisuride SPECT in degenerative extrapyramidal diseases , 2001, Nuclear medicine communications.

[13]  K. Gucuyener,et al.  Is increased D2 receptor availability associated with response to stimulant medication in ADHD , 2001, Developmental medicine and child neurology.

[14]  D. Nutt,et al.  New insights into the role of the GABAA–benzodiazepine receptor in psychiatric disorder , 2001, British Journal of Psychiatry.

[15]  L. A. Noorduyn,et al.  Estrogen receptor status in primary breast cancer: iodine 123-labeled cis-11beta-methoxy-17alpha-iodovinyl estradiol scintigraphy. , 2001, Radiology.

[16]  Roger N Gunn,et al.  In-vivo measurement of activated microglia in dementia , 2001, The Lancet.

[17]  F. Yurt,et al.  New radiolabeled CCK-8 analogues [Tc-99m-GH-CCK-8 and Tc-99m-DTPA-CCK-8]: preparation and biodistribution studies in rats and rabbits. , 2001, Nuclear medicine and biology.

[18]  H. Strauss,et al.  Detection of Monocyte Chemoattractant Protein-1 Receptor Expression in Experimental Atherosclerotic Lesions: An Autoradiographic Study , 2001, Circulation.

[19]  F. Blankenberg,et al.  Imaging macrophages and the apoptosis of granulocytes in a rodent model of subacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1 and annexin V , 2001, European Journal of Nuclear Medicine.

[20]  T. Hirai,et al.  Serial evaluation of fatty acid metabolism in rats with myocardial infarction by pinhole SPECT , 2001, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[21]  E. Krenning,et al.  Procedure guideline for somatostatin receptor scintigraphy with (111)In-pentetreotide. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[22]  E. Ringelstein,et al.  Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy , 2001, Journal of Neurology.

[23]  M. Béhé,et al.  Imaging tumors with peptide-based radioligands. , 2001, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[24]  T. Visser,et al.  Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives , 2001, European Journal of Nuclear Medicine.

[25]  Sibylle Ziegler,et al.  Noninvasive Imaging of αvβ3 Integrin Expression Using 18F-labeled RGD-containing Glycopeptide and Positron Emission Tomography , 2001 .

[26]  Y. D'Asseler,et al.  99Tcm labelled HL91 versus computed tomography and biopsy for the visualization of tumour recurrence of squamous head and neck carcinoma , 2001 .

[27]  M Schwaiger,et al.  Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  Magdalena Rafecas,et al.  A prototype high-resolution animal positron tomograph with avalanche photodiode arrays and LSO crystals , 2001, European Journal of Nuclear Medicine.

[29]  W. Oyen,et al.  Radiopharmaceuticals for scintigraphic imaging of infection and inflammation , 2001, Inflammation Research.

[30]  G. Slegers,et al.  Synthesis and in vitro evaluation of 123I-labelled human recombinant annexin V. , 2001, Biomolecular engineering.

[31]  Y. D'Asseler,et al.  99Tc(m) labelled HL91 versus computed tomography and biopsy for the visualization of tumour recurrence of squamous head and neck carcinoma. , 2001, Nuclear medicine communications.

[32]  G. Hanks,et al.  Single-photon emission computed tomography and positron-emission tomography assays for tissue oxygenation. , 2001, Seminars in radiation oncology.

[33]  J. Booij,et al.  [123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease , 2001, Journal of Neural Transmission.

[34]  B Walder,et al.  Similarity and Robustness of PET and SPECT Binding Parameters for Benzodiazepine Receptors , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[35]  A. Alavi,et al.  Role of radionuclide imaging in trials of antiangiogenic therapy. , 2000, Academic radiology.

[36]  Stanley J. Wiegand,et al.  Vascular-specific growth factors and blood vessel formation , 2000, Nature.

[37]  P. Doevendans,et al.  Visualisation of cell death in vivo in patients with acute myocardial infarction , 2000, The Lancet.

[38]  A. Buchan,et al.  Somatostatin receptor subtype expression and function in human vascular tissue. , 2000, American journal of physiology. Heart and circulatory physiology.

[39]  H. Hydén,et al.  A receptor for phosphatidylserine-speci ® c clearance of apoptotic cells , 2000 .

[40]  J. Mountz,et al.  Noninvasive monitoring of gene transfer using a reporter receptor imaged with a high-affinity peptide radiolabeled with 99mTc or 188Re. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[41]  G. Schroth,et al.  Imaging the rat brain on a 1.5 T clinical MR-scanner , 2000, Journal of Neuroscience Methods.

[42]  J Konishi,et al.  Evaluation of myocardial infarct size in rat heart by pinhole SPECT , 2000, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[43]  E C Frey,et al.  Receiver operating characteristic evaluation of iterative reconstruction with attenuation correction in 99mTc-sestamibi myocardial SPECT images. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[44]  A. Signore,et al.  123I-interleukin-2 scintigraphy for in vivo assessment of intestinal mononuclear cell infiltration in Crohn's disease. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[45]  J. Blum Receptor radiopharmaceuticals: biomolecular nuclear medicine , 2000, European Journal of Nuclear Medicine.

[46]  M J Paulus,et al.  High resolution X-ray computed tomography: an emerging tool for small animal cancer research. , 2000, Neoplasia.

[47]  A. Rauth,et al.  BRU59-21, a second-generation 99mTc-labeled 2-nitroimidazole for imaging hypoxia in tumors. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[48]  Okarvi Sm Recent developments in 99Tcm-labelled peptide-based radiopharmaceuticals: an overview. , 1999 .

[49]  P. Vaupel,et al.  Hypoxic cervical cancers with low apoptotic index are highly aggressive. , 1999, Cancer research.

[50]  P. Meltzer,et al.  Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. , 1999, The American journal of pathology.

[51]  J. Seibyl,et al.  Quantitation of benzodiazepine receptor binding with PET [11C]iomazenil and SPECT [123I]iomazenil: preliminary results of a direct comparison in healthy human subjects , 1999, Psychiatry Research: Neuroimaging.

[52]  S. Cherry,et al.  Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[53]  Horst Kessler,et al.  Radiolabeled αvβ3 Integrin Antagonists: A New Class of Tracers for Tumor Targeting , 1999 .

[54]  D. Cheresh,et al.  The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. , 1999, The Journal of clinical investigation.

[55]  D. Weber,et al.  Ultra-high-resolution imaging of small animals: Implications for preclinical and research studies , 1999, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[56]  G. Semenza,et al.  Oncogenic alterations of metabolism. , 1999, Trends in biochemical sciences.

[57]  M. Schwaiger,et al.  Radiolabeled alpha(v)beta3 integrin antagonists: a new class of tracers for tumor targeting. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[58]  J. Reubi,et al.  Expression of somatostatin receptors in peritumoral veins of human tumors , 1999, Cancer.

[59]  S. Okarvi Recent developments in 99Tcm-labelled peptide-based radiopharmaceuticals: an overview. , 1999, Nuclear medicine communications.

[60]  J. Savill,et al.  Phagocytosis triggers macrophage release of Fas ligand and induces apoptosis of bystander leukocytes. , 1999, Journal of immunology.

[61]  K. D. de Bruin,et al.  New iodinated progestins as potential ligands for progesterone receptor imaging in breast cancer. Part 2: In vivo pharmacological characterization. , 1998, Nuclear medicine and biology.

[62]  M. Waterfield,et al.  The CC Chemokine Monocyte Chemotactic Peptide-1 Activates both the Class I p85/p110 Phosphatidylinositol 3-Kinase and the Class II PI3K-C2α* , 1998, The Journal of Biological Chemistry.

[63]  R G Blasberg,et al.  Tumor growth modulation by sense and antisense vascular endothelial growth factor gene expression: effects on angiogenesis, vascular permeability, blood volume, blood flow, fluorodeoxyglucose uptake, and proliferation of human melanoma intracerebral xenografts. , 1998, Cancer research.

[64]  R. Doms,et al.  Influence of the CCR2-V64I Polymorphism on Human Immunodeficiency Virus Type 1 Coreceptor Activity and on Chemokine Receptor Function of CCR2b, CCR3, CCR5, and CXCR4 , 1998, Journal of Virology.

[65]  M. Suga,et al.  Measurement of serum monocyte chemoattractant protein-1 and its clinical application for estimating the activity of granuloma formation in sarcoidosis. , 1998, Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG.

[66]  J. Tiihonen,et al.  Fentanyl decreases β‐CIT binding to the dopamine transporter , 1998, Synapse.

[67]  K. D. de Bruin,et al.  Synthesis, estrogen receptor binding, and tissue distribution of a new iodovinylestradiol derivative (17alpha,20E)-21-[123I]Iodo-11beta-nitrato-19-norp regna-1,3,5 (10),20-tetraene-3,17-diol (E-[123I]NIVE). , 1998, Nuclear medicine and biology.

[68]  W. Oertel,et al.  Time course of chemokines in the cerebrospinal fluid and serum during herpes simplex type 1 encephalitis , 1998, Journal of the Neurological Sciences.

[69]  G. Semenza Hypoxia-inducible factor 1 and the molecular physiology of oxygen homeostasis. , 1998, The Journal of laboratory and clinical medicine.

[70]  N. Weidner,et al.  Tumoural vascularity as a prognostic factor in cancer patients: the evidence continues to grow , 1998, The Journal of pathology.

[71]  C. Bachert,et al.  Cytokines and Adhesion Molecules in Allergic Rhinitis , 1998, American journal of rhinology.

[72]  S. Barrington,et al.  Technetium-99m-labeled HL91 to identify tumor hypoxia: correlation with fluorine-18-FDG. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[73]  C. Reutelingsperger,et al.  Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. , 1998, Cytometry.

[74]  R. Bravo,et al.  Defects in Macrophage Recruitment and Host Defense in Mice Lacking the CCR2 Chemokine Receptor , 1997, The Journal of experimental medicine.

[75]  S Weber,et al.  The design of an animal PET: flexible geometry for achieving optimal spatial resolution or high sensitivity , 1997, IEEE Transactions on Medical Imaging.

[76]  J. Carrasquillo,et al.  Biodistribution of 125I-labeled des(1-3) insulin-like growth factor I in tumor-bearing nude mice and its in vitro catabolism. , 1997, Cancer research.

[77]  D. Agrawal,et al.  Morphological and biochemical characterization and analysis of apoptosis. , 1997, Journal of pharmacological and toxicological methods.

[78]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[79]  D. Graves,et al.  The pattern of monocyte recruitment in tumors is modulated by MCP-1 expression and influences the rate of tumor growth. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[80]  J. Savill Apoptosis in resolution of inflammation , 1997, Journal of leukocyte biology.

[81]  E. Engvall,et al.  Integrins and vascular extracellular matrix assembly. , 1997, The Journal of clinical investigation.

[82]  L. Gesualdo,et al.  Monocyte chemotactic peptide-1 expression and monocyte infiltration in acute renal transplant rejection. , 1997, Transplantation.

[83]  Erkki Ruoslahti,et al.  αv Integrins as receptors for tumor targeting by circulating ligands , 1997, Nature Biotechnology.

[84]  Pamela F. Jones,et al.  Isolation of Angiopoietin-1, a Ligand for the TIE2 Receptor, by Secretion-Trap Expression Cloning , 1996, Cell.

[85]  E. Abel Clinical applications of research on angiogenesis , 1996 .

[86]  A. Rauth,et al.  In vitro and in vivo evaluation of a technetium-99m-labeled 2-nitroimidazole (BMS181321) as a marker of tumor hypoxia. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[87]  S. Vallabhajosula,et al.  Preclinical evaluation of technetium-99m-labeled somatostatin receptor-binding peptides. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[88]  B. Rollins Monocyte chemoattractant protein 1: a potential regulator of monocyte recruitment in inflammatory disease. , 1996, Molecular medicine today.

[89]  S. Vallabhajosula,et al.  Technetium-99m-white blood cell-specific imaging agent developed from platelet factor 4 to detect infection. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[90]  K. Fujikawa,et al.  Preparation and characterization of a disulfide-linked bioconjugate of annexin V with the B-chain of urokinase: an improved fibrinolytic agent targeted to phospholipid-containing thrombi. , 1996, Biochemistry.

[91]  E S Gragoudas,et al.  Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. , 1996, Archives of ophthalmology.

[92]  F. Sarkar,et al.  Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. , 1995, The Journal of clinical investigation.

[93]  E. Keystone,et al.  Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)‐1β production by synovial T cells , 1995, Clinical and experimental immunology.

[94]  U. Ikeda,et al.  Induction of monocyte chemoattractant protein-1 synthesis in human monocytes during transendothelial migration in vitro. , 1995, Circulation research.

[95]  C. Thompson,et al.  Apoptosis in the pathogenesis and treatment of disease , 1995, Science.

[96]  C. Reutelingsperger,et al.  The Complexity of the Phospholipid Binding Protein Annexin V , 1995, Thrombosis and Haemostasis.

[97]  J. Folkman,et al.  Hypoxic induction of endothelial cell growth factors in retinal cells: identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. , 1995, Molecular medicine.

[98]  D. Leroith,et al.  Insulin-like Growth Factors and Cancer , 1995, Annals of Internal Medicine.

[99]  D. Cheresh,et al.  Integrin α v β 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels , 1994, Cell.

[100]  D. Cheresh,et al.  Integrin alpha v beta 3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[101]  J Engel,et al.  Selective recognition of cyclic RGD peptides of NMR defined conformation by alpha IIb beta 3, alpha V beta 3, and alpha 5 beta 1 integrins. , 1994, The Journal of biological chemistry.

[102]  W. Eckelman The application of receptor theory to receptor-binding and enzyme-binding oncologic radiopharmaceuticals. , 1994, Nuclear medicine and biology.

[103]  D. Cheresh,et al.  Requirement of vascular integrin alpha v beta 3 for angiogenesis. , 1994, Science.

[104]  J. Laissue,et al.  High density of somatostatin receptors in veins surrounding human cancer tissue: Role in tumor‐host interaction? , 1994, International journal of cancer.

[105]  D. Cheresh,et al.  Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. , 1994, Cell.

[106]  A. Mantovani,et al.  Species-specificity of monocyte chemotactic protein-1 and -3. , 1994, Cytokine.

[107]  E. Brogi,et al.  Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. , 1994, Circulation.

[108]  A. Fischman,et al.  Technetium-99m-labeled chemotactic peptides: comparison with indium-111-labeled white blood cells for localizing acute bacterial infection in the rabbit. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[109]  A. Fischman,et al.  In vivo bioactivity and biodistribution of chemotactic peptide analogs in nonhuman primates. , 1993, Journal of Nuclear Medicine.

[110]  T. Moody,et al.  Growth factor and peptide receptors in small cell lung cancer. , 1993, Life sciences.

[111]  R. Timpl,et al.  Conformation/activity studies of rationally designed potent anti-adhesive RGD peptides. , 1992, European journal of biochemistry.

[112]  L. Golberg,et al.  Non-invasive assessment of human tumour hypoxia with 123I-iodoazomycin arabinoside: preliminary report of a clinical study. , 1992, British Journal of Cancer.

[113]  E. Krenning,et al.  The role of somatostatin and its analogs in the diagnosis and treatment of tumors. , 1991, Endocrine reviews.

[114]  M. Mintun,et al.  Positron Tomographic Assessment of 16α-[18F] Fluoro-17β-Estradiol Uptake in Metastatic Breast Carcinoma , 1991 .

[115]  E. Woltering,et al.  Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane. , 1991, The Journal of surgical research.

[116]  D. Cheresh Structure, function and biological properties of integrin alpha v beta 3 on human melanoma cells. , 1991, Cancer metastasis reviews.

[117]  L. Kvols,et al.  Distribution of somatostatin receptors in normal and tumor tissue. , 1990, Metabolism: clinical and experimental.

[118]  G. Denardo,et al.  Quo vadis radioimmune imaging? , 1990, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[119]  C. Heldin,et al.  Platelet-derived growth factor: mechanism of action and possible in vivo function. , 1990, Cell regulation.

[120]  M. Niwa,et al.  Partial characterization of insulin-like growth factor I in primary human lung cancers using immunohistochemical and receptor autoradiographic techniques. , 1990, Cancer research.

[121]  S. Wahl,et al.  Inflammation and Repair , 1990 .

[122]  K. Hall,et al.  Growth factors : from genes to clinical application , 1990 .

[123]  A. Young,et al.  Synthesis of a high specific activity 125I-labeled analog of PK 11195, potential agent for SPECT imaging of the peripheral benzodiazepine binding site. , 1989, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[124]  J. Penney,et al.  Isoquinoline and peripheral-type benzodiazepine binding in gliomas: implications for diagnostic imaging. , 1988, Cancer research.

[125]  Daniel L. Feeback,et al.  Inflammation and Repair , 1987 .

[126]  B. Rasmussen,et al.  BENEFICIAL EFFECT OF ADJUVANT TAMOXIFEN THERAPY IN PRIMARY BREAST CANCER PATIENTS WITH HIGH OESTROGEN RECEPTOR VALUES , 1985, The Lancet.

[127]  J. Mendelsohn,et al.  Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[128]  S. Reichlin Somatostatin (First of two parts) , 1983 .

[129]  H. Wagner,et al.  Localization of Abscess with an Iodinated Synthetic Chemotactic Peptide , 1982, Nuklearmedizin.

[130]  J. Folkman Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[131]  J Folkman,et al.  Transplacental carcinogenesis by stilbestrol. , 1971, The New England journal of medicine.