The Chemistry of Molecular Imaging

Preface ix

List of Contributors xi

1 An Introduction to Molecular Imaging 1
Ga-Lai Law and Wing-Tak Wong

1.1 Introduction 1

1.2 What is Positron Emission Tomography (PET)? 3

1.3 What is Single Photon Emission Computed Tomography (SPECT)? 6

1.4 What is Computed Tomography (CT) or Computed Axial Tomography (CAT)? 8

1.5 What is Magnetic Resonance Imaging (MRI)? 11

1.6 What is Optical Imaging? 15

1.7 What is Ultrasound (US)? 19

1.8 Conclusions 22

References 24

2 Chemical Methodology for Labelling and Bioconjugation 25
Lina Cui and Jianghong Rao

2.1 Introduction 25

2.2 Chemical Methods 25

2.3 Site-Specific Modification of Proteins or Peptides 36

2.4 Conclusions 45

References 45

3 Recent Developments in the Chemistry of [18F]Fluoride for PET 55
Dirk Roeda and Frédéric Dollé

3.1 Introduction 55

3.2 Fluorine-18: The Starting Material 56

3.3 Reactive [18F]Fluoride 56

3.4 The Radiofluorination 58

3.5 Labelling of Large Biological Molecules 65

3.6 Conclusions 70

References 70

4 Carbon-11 Nitrogen-13 and Oxygen-15 Chemistry: An Introduction to Chemistry with Short-Lived Radioisotopes 79
Philip W. Miller Koichi Kato and Bengt Långström

4.1 Introduction 79

4.2 Carbon-11 Chemistry 81

4.3 Nitrogen-13 Chemistry 93

4.4 Oxygen-15 Chemistry 98

4.5 Conclusions 99

References 99

5 The Chemistry of Inorganic Nuclides (86Y 68Ga 64Cu 89Zr 124I) 105
Eric W. Price and Chris Orvig

5.1 Introduction: Inorganic Nuclide-Based Radiopharmaceuticals 105

5.2 Radiopharmaceutical Design 107

5.3 Radiopharmaceutical Stability 108

5.4 86Yttrium Radiometal Ion Properties 110

5.5 68Gallium Radiometal Ion Properties 116

5.6 64Copper Radiometal Ion Properties 120

5.7 89Zirconium Radiometal Ion Properties 123

5.8 124Iodine Nuclide Properties 125

5.9 Conclusions 129

References 129

6 The Radiopharmaceutical Chemistry of Technetium and Rhenium 137
Jonathan R. Dilworth and Sofia I. Pascu

6.1 Introduction 137

6.2 Technetium and Rhenium Radiopharmaceutical Chemistry 139

6.3 Technetium and Rhenium(IV) 149

6.4 Technetium and Rhenium(III) 149

6.5 Technetium and Rhenium(I) 151

6.6 Imaging of Hypoxia with 99mTc 155

6.7 Technetium and Rhenium Diphosphonate Complexes 157

6.8 The Future for Technetium and Rhenium Radiopharmaceuticals 157

References 158

7 The Radiopharmaceutical Chemistry of Gallium(III) and Indium(III) for SPECT Imaging 165
Jonathan R. Dilworth and Sofia I. Pascu

7.1 Introduction to Gallium and Indium Chemistry 165

7.2 Gallium and Indium Complexes and Related Bioconjugates 166

7.3 Auger Electron Therapy with 111Indium 175

7.4 Prospects for 67Ga and 111In Radiochemistry 176

References 176

8 The Chemistry of Lanthanide MRI Contrast Agents 179
Stephen Faulkner and Octavia A. Blackburn

8.1 Introduction 179

8.2 Gadolinium Complexes as MRI Contrast Agents 180

8.3 Minimising the Toxicity of Gadolinium Contrast Agents 184

8.4 Rationalising the Behaviour of MRI Contrast Agents 185

8.5 Strategies for Increasing Relaxivity 188

8.6 Responsive MRI 192

8.7 Conclusions and Prospects 195

References 195

9 Nanoparticulate MRI Contrast Agents 199
Juan Gallo and Nicholas J. Long

9.1 Introduction 199

9.2 T2 Contrast Agents 200

9.3 T1 Contrast Agents 203

9.4 T1-T2 Dual MRI Contrast Agents 208

9.5 Water Solubilisation 209

9.6 Functionalisation and Surface Modification 213

9.7 Applications 216

9.8 Conclusions and Outlook 220

References 220

10 CEST and PARACEST Agents for Molecular Imaging 225
Osasere M. Evbuomwan Enzo Terreno Silvio Aime and A. Dean Sherry

10.1 Introduction 225

10.2 Diamagnetic CEST Agents 226

10.3 Paramagnetic Chemical Exchange Saturation Transfer (PARACEST) Agents 229

10.4 Responsive PARACEST Agents 230

10.5 In Vivo Detection of PARACEST Agents 233

10.6 Supramolecular CEST Agents 235

10.7 LipoCEST Agents 236

10.8 Conclusions 241

References 241

11 Organic Molecules for Optical Imaging 245
Michael Hon-Wah Lam Ga-Lai Law Chi-Sing Lee and Ka-Leung Wong

11.1 Introduction 245

11.2 Designing Molecular Probes for Bio-imaging 246

11.3 Different Types of Organic-based Chromophores and Fluorophores for Bioimaging 249

11.4 Mechanisms of Photophysical Processes and Their Applications in Molecular Imaging and Chemosensing 258

11.5 Two/Multi-photon Induced Emission and In Vitro / In Vivo Imaging 262

11.6 Time-Resolved Imaging 266

11.7 Bioluminescence in Molecular Imaging 267

11.8 Photoacoustic Imaging 269

11.9 Conclusion and Future Perspectives 270

References 270

12 Application of d- and f-Block Fluorescent Cell Imaging Agents 275
Michael P. Coogan and Simon J. A. Pope

Abbreviations 275

12.1 Introduction 275

12.2 d6 Metal Complexes in Fluorescent Cell Imaging 277

12.3 f-Block Imaging Agents 285

12.4 Conclusions 296

References 296

13 Lanthanide-Based Upconversion Nanophosphors for Bioimaging 299
Fuyou Li Wei Feng Jing Zhou and Yun Sun

13.1 Introduction 299

13.2 Fabrication of Ln-UCNPs Suitable for Bioimaging 299

13.3 Surface Modification of Ln-UCNPs 304

13.4 In Vivo Imaging Applications 306

13.5 Biodistribution and Toxicity of UCNPs 316

13.6 Future Directions 317

References 317

14 Microbubbles: Contrast Agents for Ultrasound and MRI 321
April M. Chow and Ed X. Wu

14.1 Introduction 321

14.2 Classification of Microbubbles 321

14.3 Applications in Ultrasound Imaging 324

14.4 Applications in Magnetic Resonance Imaging 327

14.5 Applications beyond US Imaging and MRI 330

14.6 Conclusions: Limitations Bioeffects and Safety 330

References 331

15 Non-Nanoparticle-Based Dual-Modality Imaging Agents 335
Reinier Hernandez Tapas R. Nayak Hao Hong and Weibo Cai

15.1 Introduction 335

15.2 PET/Optical Agents 336

15.3 SPECT/Optical Agents 341

15.4 MRI/Optical Agents 345

15.5 PET/MRI Agents 348

15.6 Conclusions 348

References 350

16 Chemical Strategies for the Development of Multimodal Imaging Probes Using Nanoparticles 355
Amanda L. Eckermann Daniel J. Mastarone and Thomas J. Meade

16.1 Introduction 355

16.2 Fluorescence-MRI 357

16.3 Near-Infrared Fluorescence/MRI 359

16.4 NIR-PET 368

16.5 Upconversion Luminescence 372

16.6 PET-SPECT-CT-MRI 376

16.7 Ultrasound 382

16.8 Magnetomotive Optical Coherence Tomography (MM-OCT) 383

16.9 Photoacoustic Imaging 384

16.10 Conclusions 384

References 385

Index 389