Molecular Imaging of the Lungs

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ISBN: 9781574448542 | 1574448544
Cover: Hardcover
Copyright: 5/23/2005

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This authoritative reference reviews current and emerging airway imaging modalities that may impact the detection and treatment of airway diseases--reviewing applications in expression and inflammation imaging, the imaging of pulmonary cytokine regulation, the molecular imaging of lung cancer, and the imaging of cell death.

Introduction

iii

Preface

Contributors

SECTION 1: METHODOLOGIES

1. Molecular Imaging Probes for PET and SPECT

(38)

Raffaella Rossin and Michael J. Welch

I. Introduction

(3)

II. Radionuclides for PET and SPECT Molecular Imaging Probes

(6)

III. Radiotracers for Molecular Imaging

(12)

A. Tumor Metabolism

(2)

B. Tumor Proliferation

(2)

C. Tumor Hypoxia

(2)

D. Tumor Receptors

(1)

SST Receptors

(1)

VIP Receptors

(1)

Other Receptors

(1)

E. Reporter Genes

(2)

IV. Summary

(1)

References

(16)

2. "Micro"-Instruments for Molecular Imaging with PET and SPECT

(18)

Richard LaForest

I. Introduction

(2)

II. Single Photon Emission Computed Tomography

(3)

III. Positron Emission Tomography

(8)

IV. Combined Systems

(1)

V. Conclusions

(1)

References

(4)

3. PET and SPECT as Platforms for Molecular Imaging

(36)

Buck E. Rogers

I . Introduction

(1)

II. SPECT Imaging

(4)

A. Principles of SPECT Imaging

(2)

B. Radionuclides Used in SPECT Imaging

(2)

IIII. PET Imaging

(3)

A. Principles of PET Imaging

(2)

B. Radionuclides Used in PET Imaging

(1)

IV. SPECT Imaging vs. PET Imaging

(2)

V. Applications of PET and SPECT Molecular Imaging

(11)

A. Imaging of RNA

(2)

B. Imaging of Endogenous Proteins and Protein Function

(1)

Imaging of Intracellular Proteins

(1)

Imaging of Transmembrane Proteins

(4)

C. Imaging of Exogenous Marker Genes

(1)

Herpes Simplex Virus-1 Thymidine Kinase

(1)

Sodium Iodide Symporter

(1)

Somatostatin Receptor Subtype 2

(1)

Dopamine-2 Receptor

(1)

VI. Summary

(1)

Acknowledgments

(1)

References

(14)

4. Imaging Cellular and Molecular Processes in the Lung Using Bioluminescent Reporter Genes

(18)

Christopher H. Contag

I. Overview

(1)

II. Introduction

(2)

III. Luciferase and Related Proteins

(4)

A. Coeloptera Luciferases

(2)

B. Luciferases from Marine Organisms

100

(1)

C. Bacterial Luciferases

100

(2)

D. Other Luciferases

102

(1)

IV. Luciferins and Biodistribution In Vivo

102

(1)

V. Instrumentation Used in BLI

103

(1)

VI. Multifunctional Reporter Genes

104

(1)

VII. Validation of In Vivo Data Using Ex Vivo Assays

105

(1)

VIII. Applications of BLI in the Lung

105

(3)

A. Monitoring Infection of the Lung

105

(1)

B. Lung Metastasis

106

(1)

C. Gene Transfer to the Lung

106

(2)

IX. Summary and Future Outlook

108

(1)

Aknowledgments

108

(1)

References

108

(5)

5. Magnetic Resonance Imaging

113

(22)

Joel R. Garbow, Cassandra B. Orellana, and Jeffrey J. Neil

I. Introduction

114

(1)

II. Molecular MRI

115

(4)

A. Traditional CAs

115

(1)

B. Organ-Specific CAs

116

(1)

C. Targeted CAs

116

(1)

D. Activated CAs

116

(1)

E. Targeting Cellular Markers

117

(1)

F. Imaging Transgene Expression

117

(2)

G. Switchable CAs

119

(1)

H. Imaging Gene Products

119

(1)

III. MRI of Lung

119

(9)

A. Proton Imaging

120

(1)

B. Hyperpolarized Gas Imaging

121

(3)

C. Diffusion

124

(1)

D. Ventilation Imaging

125

(2)

E. Intrapulmonary pAO2

127

(1)

F. Perfusion Imaging

127

(1)

IV. Future Prospects

128

(1)

Acknowledgment

128

(1)

References

128

(7)

6. Imaging the Mouse Lung with Micro-CT

135

(36)

Wolfgang Recheis, Geoffrey McLennan, Alan F. Ross, Eric A. Hoffman, Ann V. Clough, and Steven T. Haworth

I. Introduction

136

(1)

II. Technical Principals and Overview of Micro-CT

137

(15)

A. Micro-CT Introduction

138

(2)

B. Micro-Focal Sources of X-ray Production

140

(1)

C. Filters

140

(3)

D. Some Detector Characteristics

143

(2)

E. Comments on Dose Exposure

145

(1)

F. Resolution of the Systems

146

(1)

G. Tomographic Reconstruction

147

(1)

H. Ring Artifact Reduction

148

(1)

I. Beam Hardening

149

(2)

J. Hounsfield Unit Calibration

151

(1)

K. Commercially Available Systems

151

(1)

III. Small Animal Lung Imaging

152

(14)

A. Optimized In Situ and In Vivo Mouse Lung Protocol

154

(1)

In Situ Scanning Protocols

154

(1)

In Vivo Scanning Protocols

156

(1)

B. Examination of Lung Tissue Samples from Larger Animals

156

(2)

C. Dynamic Imaging: Microfluoroscopy Coupled to Micro-CT

158

(5)

D. Conclusions

163

(3)

References

166

(5)

7. Noninvasive Imaging Strategies to Visualize Tissue-Specific Gene Expression Using Transcriptional Amplification Approaches

171

(38)

Meera Iyer and Sanjiv S. Gambhir

I. Introduction

172

(1)

II. GAL4 Transactivating System

172

(4)

III. Tissue-Specific Promoters

176

(1)

IV. Strategies to Enhance Transcriptional Activation of Weak, Tissue-Specific Promoters

177

(4)

V. Role of Molecular Imaging in the Noninvasive Monitoring of Gene Expression In Vivo

181

(4)

VI. Gene Therapy Vectors

185

(5)

A. Adenoviruses

185

(2)

B. Adeno-Associated Virus

187

(1)

C. Retroviruses

187

(1)

D. Lentiviruses

187

(1)

E. Nonviral Vectors

188

(2)

VII. Imaging Pulmonary Gene Expression In Vivo

190

(4)

VIII. Transgenic Mouse Models

194

(2)

IX. Conclusion

196

(1)

References

196

(13)

SECTION 2: APPLICATION TO THE LUNGS

8. Pulmonary Transgene Expression Imaging

209

(28)

Daniel P. Schuster

I. Introduction

210

(1)

II. Platforms for Gene Expression Imaging

210

(3)

A. Radionuclide-Based Methods

210

(1)

PET

210

(1)

Non-PET

211

(1)

B. Optical Imaging

211

(1)

C. Magnetic Resonance Imaging

212

(1)

III. Strategies for Gene Expression Imaging

213

(6)

A. Endogenous Gene Expression

213

(1)

B. Exogenous Gene Expression

214

(1)

C. PET Imaging for Reporter Gene Expression

214

(5)

IV. Gene Expression Studies of the Lungs with PET

219

(10)

A. PET Imaging to Detect the Time-Course of Transgene Expression in the Lungs

219

(2)

B. PET Imaging to Evaluate Methods of Vector Delivery to the Lungs

221

(1)

C. PET Imaging to Evaluate the Intrapulmonary Distribution of Transgene Expression

222

(2)

D. Quantitation of Reporter Gene Expression in the Lungs with PET Imaging

224

(5)

V. Applications

229

(1)

References

230

(7)

9. Inflammation Imaging in the Lungs

237

(22)

Hazel A. Jones

I. Introduction

237

(2)

II. Lung Water

239

(1)

III. Amine Kinetics

239

(1)

IV. Components of the Pulmonary Inflammatory Process

240

(13)

A. Adhesion Molecule Expression

240

(1)

B. White Cell Trafficking

241

(1)

C. In Vivo Cell Labeling

242

(1)

D. Neutrophil Activation

242

(6)

E. Macrophage Kinetics

248

(4)

F. Resolution of Inflammation

252

(1)

V. Progression of Lung Disease

253

(1)

A. Fibroblast Proliferation

253

(1)

B. Control of the Extracellular Matrix

253

(1)

C. Synthesis of Matrix Proteins

253

(1)

D. Extracellular Matrix Degradation

254

(1)

VI. Summary

254

(1)

References

255

(4)

10. Bioluminescence Imaging of Transcription Factor Activity in the Lungs

259

(1)

E. Duco Jansen and Timothy S. Blackwell

I. Introduction

260

(1)

II. Imaging Methodology

260

(6)

A. Bioluminescent Reaction

260

(1)

B. Tissue Optics

261

(4)

C. Imaging System Design and Function

265

(1)

III. Applications

266

(10)

A. Transcription Factors and the Lungs

266

(1)

B. Detection of NF-kB Activation in Reporter Mice

267

(4)

C. NF-kB Activation in Disease Models

271

(1)

Lung Inflammation Induced by Bacterial LPS

271

(1)

Lung Inflammation Following Direct Hepatic Injury and Pancreatitis

273

(1)

Pseudomonas Pneumonia

274

(1)

Gene Therapy to Modulate NF-KB Activation

274

(2)

D. Summary

276

(1)

IV. Challenges and Future Directions

276

(3)

References

279

(6)

11. Molecular Imaging of Lung Cancer

285

(1)

Philipp Mayer-Kuckuk, Michael Doubrovin, Irma Serganova, and Ronald G. Blasberg

I. Molecular Imaging Strategies

286

(7)

A. Direct Imaging

286

(2)

B. Indirect Imaging

288

(3)

C. Biomarker Imaging

291

(2)

II. Oncogenic Cell Transformation

293

(4)

A. The Study of Lung Cancer in Experimental Mouse Models

295

(1)

B. Genetic Mouse Models of Lung Cancer

295

(2)

III. Imaging Oncogenesis in Genetic Mouse Models

297

(1)

IV. Imaging Oncogenesis Pathways

298

(5)

V. Imaging Tumor Treatment

303

(2)

Acknowledgments

305

(1)

References

305

(8)

12. Molecular Imaging of Protein-Protein Interactions in Living Animals

313

(1)

David Piwnica-Worms, Kathryn E. Luker, and Victor M. Villalobos

I. Introduction

313

(2)

II. Detecting Protein Interactions in Intact Cells and Animals

315

(6)

A. Two-Hybrid

315

(2)

B. Protein-Fragment Complementation

317

(2)

C. Other Strategies

319

(2)

III. Applications In Vivo

321

(1)

IV. Concluding Comments

322

(1)

Acknowledgments

323

(1)

References

323

(4)

13. Functional Imaging of Cellular Death

327

(1)

Robert H. Mach

I. Introduction

327

(1)

II. Apoptosis vs. Necrosis

328

(3)

III. The Need to Discriminate Between Apoptosis and Necrosis

331

(2)

IV. Measurement of Apoptosis and Necrosis In Vitro

333

(2)

V. Measurement of Apoptosis and Necrosis In Vivo Using Functional Imaging Techniques

335

(8)

A. Radiolabeled Annexin V Analogs

336

(4)

B. Imaging Agents Based on Caspase-3

340

(2)

C. Imaging PARP- 1 Activity in Cells Undergoing Necrosis

342

(1)

VI. Imaging Cell Death During Lung Health and Disease

343

(2)

VII. Conclusion

345

(1)

Acknowledgments

345

(1)

References

345

(4)

14. Imaging Cell Trafficking

349

(1)

Naoto Oku and Tomohiro Asai

I. Introduction

349

(2)

II. Relationship Between Tumor Cell Trafficking and Metastatic Potential

351

(2)

III. Involvement of Cell Adhesion Molecules in Metastatic Cell Trafficking

353

(4)

IV. Determination of Intraorgan Trafficking of Metastatic Cells

357

(1)

V. Topological Distribution of Metastatic Cells as Analyzed by Whole-Body Autoradiography

358

(2)

VI. Influence of the Immune Surveillance System on Metastasis Cell Trafficking

360

(4)

VII. Conclusions and Future Prospects

364

(1)

References

364

(3)

15. Imaging Angiogenesis in the Lung

367

(1)

Wayne Mitzner and Elizabeth Wagner

I. Imaging Neovascularization in the Lung: Challenges for Measurement

367

(1)

II. Imaging Neovascularization in Asthma

368

(3)

III. Imaging Neovascularization after Pulmonary Artery Obstruction

371

(6)

IV. Imaging Neovascularization in Lung Cancer

377

(5)

V. Concluding Comments and Future Expectations

382

(1)

References

382

(3)

16. New Methods for Visualizing the Airways

385

(1)

William Lunn and Armin Ernst

I. Introduction

385

(2)

II. Cellular Evolution of Lung Cancer

387

(1)

III. Imaging Modalities

387

(8)

A. Autoflourescence Bronchoscopy

387

(3)

B. High-Magnification Bronchovideoscopy

390

(1)

C. Narrow-Band Imaging

391

(1)

D. Optical Coherence Tomography

392

(2)

E. Laser Scanning Confocal Microscopy

394

(1)

IV. Conclusions

395

(1)

References

396

(1)

17. Functional Imaging of Rodent Lungs

397

(1)

Delphine L. Chen and Daniel P. Schuster

I. Introduction

397

(1)

II. Definitions

398

(12)

A. Lung Density

398

(2)

B. Lung Volumes

400

(2)

C. Lung Water and Blood Volume Measurements

402

(1)

D. Lung Ventilation and Perfusion

403

(2)

E. PA Pressures and Right Ventricular Function

405

(4)

F. Diffusion

409

(1)

III. Conclusion

410

(1)

References

411

(4)

18. Prospects for Molecular Imaging in Humans

415

(1)

Johannes Czernin and Wolfgang Weber

I. Introduction

415

(2)

II. Molecular Imaging Assays

417

(2)

III. Imaging Targets, Probes, Processes, and Applications

419

(10)

A. Imaging Glycolytic Activity

419

(2)

B. Imaging Bone Metastases with 18F-Fluoride

421

(1)

C. Imaging Amino Acid Metabolism

422

(2)

D. Imaging Cell Membrane Synthesis

424

(2)

E. Imaging Tumor Cell Proliferation

426

(3)

IV. Using Analogs of Therapeutic Drugs as Imaging Probes

429

(1)

V. Imaging Tyrosine Kinase Receptor Densities

430

(1)

VI. Imaging the Distribution of Radiolabeled Chemotherapeutic Agents

431

(1)

VII. Imaging of the &apha;vβ3 Integrin

432

(2)

VIII. Summary

434

(1)

References

434

(7)

Index

441

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Molecular Imaging of the Lungs

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Table of Contents

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