Molecular Imaging

Basic Principles And Applications In Biomedical Research

By: Markus Rudin

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Hardcover | 12 October 2005

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564 Pages

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Molecular imaging is a rapidly emerging field that translates many concepts developed for molecular biology and cellular imaging to the in vivo imaging of intact organisms. The technique allows the study of molecular biological events in their full context and will therefore become an indispensable tool for biomedical research and drug discovery and development. This volume familiarizes the reader with the concepts of imaging and molecular imaging in particular. Basic principles of imaging technologies, reporter moieties for the various imaging modalities and the design of target reporter constructs are described in the first part. The second part illustrates how these tools can be used to visualize relevant molecular events: the biodistribution of drugs/ligands, the expression of drug targets (receptors, enzymes), and the consequences of the molecular drug-target interactions (pathway activations, system responses). A final chapter deals with visualization of cell migration (cell therapies).

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Non-Fiction Medicine Other Branches of Medicine Medical Imaging Science Physics Accident & Emergency Medicine Biology, Life Sciences Molecular Biology Booktopia Publisher Services World Scientific Publishing

Foreword	p. xvii
Acknowledgements	p. xxi
Introduction	p. 1
Biomedical Research: Elucidating Molecular Mechanisms of Disease	p. 1
Tumorigenesis as a result of multiple mutations	p. 2
Pathogenesis in Alzheimer-type dementia	p. 3
Multiple factors causing disease: Multiplexed diagnostic tools	p. 5
The Drug Discovery Process: From Target Validation to Proof-of-Concept in Man	p. 6
Imaging in Biomedical Research	p. 9
Diagnostic imaging	p. 9
Contrast-to-noise ratio and spatial resolution	p. 9
Diagnostic imaging: Detection of pathology using structural and functional readouts	p. 14
Quantification	p. 14
Target-specific or molecular imaging	p. 16
Definition: Molecular imaging	p. 16
Imaging targets	p. 17
Prerequisites for molecular imaging: Reporter constructs	p. 19
Prerequisites for molecular imaging: Imaging modalities	p. 21
Molecular imaging modalities	p. 25
Comparison of imaging modalities	p. 36
Summary	p. 37
References	p. 38
Methodologies	p. 43
Imaging Techniques	p. 45
X-Ray Computerized Tomography	p. 45
Basic principles of X-rays	p. 45
Principles of X-ray CT	p. 46
Image representation, spatial resolution, contrast-to-noise ratio	p. 51
Animal CT scanners	p. 53
Magnetic Resonance Imaging	p. 54
Interaction of a nuclear magnetic moment with a static magnetic field	p. 54
Classical description of NMR: Bloch equations and relaxation	p. 56
The NMR experiment	p. 60
Measurement of relaxation rates in FT-NMR	p. 62
Measurement of the transverse relaxation rate R[subscript 2]	p. 62
Measurement of the longitudinal relaxation rate R[subscript 1]	p. 64
Principle of magnetic resonance imaging	p. 66
Spatial encoding	p. 66
The k-space concept	p. 68
Slice selection	p. 69
Some basic image acquisition modules	p. 71
Contrast in MR images, signal enhancement by contrast agents	p. 74
In vivo magnetic resonance spectroscopy	p. 77
Animal MRI scanners	p. 81
Nuclear Imaging: Gamma Scintigraphy, Single Photon Emission Computer Tomography	p. 82
The gamma camera: Projection images	p. 83
3D gamma imaging: Single photon emission computer tomography	p. 88
SPECT scanners for animal imaging	p. 88
Positron Emission Tomography	p. 89
Physical principles of PET	p. 90
Image reconstruction	p. 94
Filtered backprojection	p. 94
Statistical image reconstruction	p. 95
3D reconstructions procedures	p. 97
High-resolution PET instrumentation	p. 99
Optical Imaging	p. 100
Photon propagation in scattering media	p. 100
The diffusion equation for light propagation in tissue	p. 100
Solutions of the diffusion equation	p. 103
Planar imaging/reflectance imaging	p. 104
Diffuse optical tomography	p. 107
Noncontact optical tomography	p. 114
Instrumentation	p. 116
Planar imaging systems	p. 116
Optical tomography systems	p. 118
Intravital microscopy	p. 118
Ultrasound Imaging	p. 120
Principles of ultrasound imaging	p. 120
Introduction, definitions	p. 120
Attenuation	p. 121
Reflection and refraction	p. 122
Scattering	p. 122
Axial and angular resolution, frame rate	p. 123
Spatial resolution	p. 124
Temporal resolution, frame rate	p. 128
Contrast enhancement	p. 128
Summary	p. 130
References	p. 132
Molecular Reporter Systems	p. 141
X-ray Contrast Agents	p. 141
Introduction	p. 141
Iodine-based contrast agents	p. 142
MRI Contrast Agents	p. 144
Factors determining the relaxivity of contrast agents	p. 144
Gadolinium-based contrast agents	p. 148
Magnetite nanoparticles	p. 152
Liposomes/micelles/microemulsions	p. 156
SPECT Radioisotopes	p. 161
Radioisotopes for gamma scintigraphy/SPECT imaging	p. 161
Technetium-99m	p. 161
Indium-111	p. 164
Iodine-123 and iodine-131	p. 165
PET Radioisotopes	p. 166
Production of radionuclides, lifetimes	p. 166
Carbon-11-labeled compounds	p. 167
Fluorine-18-labeled compounds	p. 169
Other PET nuclei	p. 173
Optical Probes: Fluorescence and Bioluminescence	p. 174
Principles of fluorescence	p. 174
Fluorescent proteins	p. 177
Fluorescent dyes	p. 179
Fluorescent nanocrystals, quantum dots	p. 182
Fluorescence energy transfer (FRET), quenching	p. 186
Bioluminescence	p. 189
Contrast Agents for Ultrasound Imaging	p. 191
Microbubbles	p. 191
Non-microbubble-based contrast agents	p. 195
Summary	p. 196
References	p. 200
Design of Molecular Imaging Probes	p. 210
Design of Target-specific Probes	p. 210
Low molecular weight probes	p. 210
Macromolecular probes: Antibodies, oligonucleotides	p. 211
Activatable probes, "smart" probes	p. 213
Change in fluorescent properties	p. 214
Change in magnetic relaxation rates	p. 218
Probe Delivery, Cell Penetration	p. 225
Cell penetrating peptides	p. 226
Receptor-mediated endocytosis	p. 230
Asialoglycoprotein receptor-mediated endocytosis	p. 231
Transferrin receptor-mediated endocytosis	p. 231
Integrin (CD11c)-mediated endocytosis	p. 233
Transfection agents	p. 234
Signal Amplification	p. 236
Increasing the payload of reporters per target	p. 236
Branched linker groups: Avidin-biotin	p. 236
Polymers with multiple reporter groups	p. 239
Trapping of reporters	p. 241
Enzymatic probe activation	p. 243
Physiological Amplification	p. 244
Summary	p. 245
References	p. 247
Applications	p. 257
Drug Imaging	p. 259
Drug Biodistribution and Pharmacokinetics	p. 259
Classical approaches in rodents: Autoradiographic studies	p. 259
In vivo studies using nuclear imaging approaches	p. 262
Labeling by radioisotopes to preserve pharmacokinetic properties	p. 262
Dose linearity	p. 263
Correction for plasma contribution	p. 264
Examples: CNS drugs	p. 264
Receptor Occupancy Studies	p. 265
Receptor binding in a homogeneous compartment	p. 266
Compartment models for estimation of tracer concentrations	p. 268
Indirect imaging or drug-receptor interactions	p. 273
Receptor occupancy studies: Examples	p. 275
Summary	p. 279
References	p. 281
Imaging Gene Expression	p. 284
Visualizing Transcription: Targeting Messenger RNA Using Labeled Antisense Oligonucleotides	p. 286
Direct Target Imaging Using Receptor-Specific Ligands	p. 292
Small molecular ligands	p. 292
Neuroendocrine tumors expressing somatostatin receptors	p. 293
Neurotransmitter systems	p. 296
Small molecule probes to study Alzheimer's disease	p. 301
Antibodies and antibody fragments	p. 307
Endovascular targets: Atherosclerosis, inflammation, tumor angiogenesis	p. 309
Tumor-specific antibody probes	p. 320
Enzymatic drug targets	p. 324
Measuring enzyme activity	p. 324
Kinases	p. 327
Proteinases	p. 331
Reporter Genes	p. 339
Reporter genes with intracellular gene products	p. 343
Reporter genes expressing membrane-associated gene products	p. 346
Dual/Multiple reporters	p. 350
Conditional or inducible reporter expression	p. 353
Using in vivo reporter gene assays for preclinical studies	p. 361
Cell marking	p. 361
Protein-protein interaction	p. 363
Gene delivery	p. 364
Summary	p. 364
References	p. 367
Imaging the Function of Gene Products	p. 387
Imaging of Signal Transduction Pathways/Protein-Protein Interaction	p. 387
Fluorescence resonance transfer	p. 389
Two-hybrid approach	p. 390
Protein fragment complementation assay	p. 393
Protein splicing	p. 395
Apoptosis	p. 397
Targeting externalized phosphatidyl-serine	p. 398
Targeting of caspases using reporter gene assays	p. 406
Phenotypic marker of apoptosis	p. 407
Metabolic/Physiological Response to Receptor Activation	p. 409
Hemodynamic changes in CNS	p. 411
Tissue energy metabolism	p. 416
Measurement of glucose utilization	p. 416
Measurement of ATP turnover	p. 424
Tissue proliferation	p. 429
DNA synthesis	p. 429
Protein synthesis	p. 431
Membrane synthesis	p. 435
Vascular permeability changes as readout of antiangiogenic therapy	p. 440
Cell signaling via second messenger	p. 446
Summary	p. 448
References	p. 450
Monitoring of Cell Migration	p. 466
Introduction	p. 466
Inflammatory Cells	p. 468
Visualization of macrophage infiltration	p. 468
Experimental models of multiple sclerosis	p. 470
Focal cerebral ischemia	p. 475
Atherosclerosis	p. 477
Solid organ transplantation	p. 480
Lymphocytes	p. 483
Stem and Progenitor Cells	p. 489
Focal cerebral ischemia	p. 490
Brain tumors	p. 494
Myocardial infarction	p. 495
Labeled Tumor Cells/Metastasis Formation	p. 498
Infectious Diseases, Gene Marking of Pathogens	p. 503
Summary	p. 505
References	p. 507
Appendices	p. 519
Physical Constants	p. 519
Mathematical Formulae	p. 520
Convolution	p. 520
Fourier transformation	p. 520
Differential equations	p. 524
Solution to coupled linear differential equations using matrix formalism	p. 524
Green's function	p. 526
Natural Amino Acids	p. 529
Nucleotides	p. 530
Index	p. 531
Table of Contents provided by Ingram. All Rights Reserved.

Molecular Imaging

Basic Principles And Applications In Biomedical Research

At a Glance

New Edition

Hardcover

Shipping

How to return your order

Defective items

You Can Find This Book In

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