Front Cover

Emerging Applications of Molecular Imaging to Oncology

Copyright

Contents

Contributors

Preface

Chapter One: Quantitative Radiology: Applications to Oncology

1. Introduction

2. Radiological Characterization of Tumors

2.1. Computed tomography

2.1.1. Structural (routine) CT

2.1.2. CT perfusion

2.1.3. Dual-energy CT

2.2. Magnetic resonance

2.2.1. Structural (routine) MR

2.2.2. MR spectroscopy and hyperpolarization

2.2.3. MR perfusion

2.2.4. Diffusion-weighted imaging

2.2.5. Diffusion tensor imaging

2.3. Positron emission tomography

3. Quantitative Radiology

3.1. Image analysis

3.1.1. Manual segmentation

3.1.2. Automated segmentation

3.1.3. Registration

3.2. Evaluation

3.3. Integration

4. Future Directions

5. Conclusion

References

Chapter Two: The Intricate Role of CXCR4 in Cancer

1. Introduction

2. CXCR4/CXCL12 Signaling

3. Expression and Physiological Functions of the CXCR4/CXCL12 Axis

4. Role of CXCR4 in Cancer

4.1. Leukemia

4.2. Multiple myeloma

4.3. Breast cancer

4.4. Prostate cancer

4.5. Ovarian cancer

4.6. Lung cancer

4.7. Gastrointestinal cancers

4.8. Renal cell carcinoma

4.9. Melanoma

4.10. Brain tumors

4.11. Soft tissue sarcomas

5. CXCR4 Antagonists as Therapeutic and Imaging Agents

6. Peptides and Peptidomimetics

6.1. CXCL12-based peptides

6.2. Synthetic peptide CXCR4 antagonists

6.3. Small cyclic peptide analogues

6.4. Antibodies against CXCR4

6.5. LMW CXCR4 antagonists

7. Conclusion

Acknowledgments

References

Chapter Three: Recent Advances in Nanoparticle-Based Nuclear Imaging of Cancers

1. Introduction

2. Lipid-Based Nanoparticles

3. Dendrimers

4. Polymers

5. Quantum Dots

6. Iron Oxide Nanoparticles

7. Gold Nanoparticles

8. Carbon Nanotubes

9. Silica-Based Nanoparticles

10. Conclusion

References

Chapter Four: Molecular-Genetic Imaging of Cancer

1. Introduction

2. Promoters

3. Reporters

4. Signal Enhancement of Reporters

4.1. Enhancers

4.2. Two-step transcriptional amplification

4.2.1. Bidirectional TSTA

4.2.2. Lentivirus-TSTA

4.2.3. Adeno-TSTA

4.2.4. Advanced TSTA system

4.2.5. Replacing components of the TSTA

4.2.6. Titratable TSTA

4.2.7. Dual TSTA

4.2.8. TSTA for imaging cellular differentiation

4.3. Codon optimization

4.4. Posttranscriptional regulatory elements

4.5. Synthetic super promoter

4.6. Introducing introns

5. Prolonged Expression of Reporters

6. Machinery for Gene Delivery

6.1. Cationic polymers (polyplexes)

6.2. Positively charged lipids (lipoplexes)

6.3. Nanoparticles (nanoplexes)

7. Size and Immunogenicity

8. Concluding Remarks

Acknowledgments

References

Chapter Five: Real-Time Fluorescence Image-Guided Oncologic Surgery

1. Introduction

1.1. Need for real-time image-guided surgery

1.2. Current methods available for image-guided surgery

1.3. Optical methods amenable to image-guided surgery

2. Fluorescence Imaging Systems for Intraoperative Procedures

2.1. Fluorescence sensor parameters

2.1.1. Quantum efficiency of a photodiode

2.1.2. Signal-to-noise ratio of an imaging sensor

2.1.3. Electrical and optical crosstalk

2.1.4. Transmission and optical density of excitation and emission filters

2.1.5. Overall SNR and contrast ratio of fluorescence signal

2.2. Optical design parameters

2.2.1. Lens and filter strategy

2.2.2. Illumination design

3. Current Intraoperative Optical Image Guidance Systems

4. Fluorescent Agents Used in Image-Guided Surgery

4.1. Endogenous fluorophores

4.2. Exogenous fluorescent agents

4.2.1. Fluorescein

4.2.2. Methylene blue

4.2.3. 5-Aminolevulinic acid

4.2.4. Indocyanine green

5. Clinical Applications of Fluorescence Image-Guided Surgery

5.1. Sentinel lymph node mapping

5.2. Tumor imaging

6. Future Directions

7. Concluding Remarks

References

Chapter Six: Cerenkov Imaging

1. Introduction

2. Cerenkov Radiation Physics (Simplified)

2.1. Dependence of CL on the refractive index of the medium

2.2. CL from α-particles

2.3. Conical wave front of Cerenkov light

2.4. Spectral characteristics of Cerenkov

2.5. Light intensity and spatial distribution

2.6. CL in tissue

3. Application of Cerenkov in Biological Sciences: CLI

3.1. CL from medical radiotracers

3.2. Instrumentation for CLI

3.3. Cerenkov luminescence tomography

3.4. Clinical Cerenkov imaging

3.5. Intraoperative Cerenkov imaging

3.6. Cerenkov to improve positron emission tomography

3.7. Cerenkov 2.0

4. Conclusion

Acknowledgments

References

Chapter Seven: Molecular Imaging of the Tumor Microenvironment for Precision Medicine and Theranostics

1. Introduction

2. Imaging and PM/Theranostics of the Physiological Microenvironment

2.1. Hypoxia

2.2. pH

3. The ECM and Its Enzymes

4. Endothelial Cells and Tumor Vasculature

5. Lymphatic Endothelial Cells, Lymphatics, and Interstitial Pressure

6. Stromal Components of the TME and Their Role in PM

7. Intraoperative Optical Imaging

8. Concluding Remarks

Acknowledgments

References

Chapter Eight: Tracking Cellular and Immune Therapies in Cancer

1. Introduction

1.1. History of cancer immunotherapy and passive versus active immunity

1.2. Immune cell subsets, the immunosuppressive microenvironment, and checkpoint inhibitors

1.3. Cellular therapies-Dendritic cell vaccines and CAR-T cells

1.4. Shortfalls of anatomic imaging for immunotherapies

2. Molecular Imaging Approaches to Cancer Immunotherapy

2.1. Approaches toward imaging the immune system

2.2. Applicable imaging modalities

3. Radionuclide Methods in the Preclinical and Clinical Settings

3.1. Direct labeling methods

3.2. Indirect imaging with reporter genes

3.3. Enzyme-based strategies

3.4. Receptor-based strategies

3.5. Transporter-based strategies

4. MRI Methods in the Preclinical and Clinical Settings

4.1. Types of MRI contrast agents

4.2. SPIO imaging

4.3. 19F MRI using perfluorocarbons

5. Opportunities for Improvements and Future Directions

5.1. Imaging the tumor immune environment prior to immune therapy

5.2. Imaging immune checkpoints

5.2.1. Cytotoxic T-lymphocyte-associated antigen 4

5.2.2. Programmed death 1

5.3. Opportunities for predicting and assessing immune responses

5.4. In vivo cell labeling progress to date

5.5. Imaging cell state with reporter genes

6. Conclusions

References

Chapter Nine: Developing MR Probes for Molecular Imaging

1. General Overview

2. T1, T2, T2* Relaxivity-Based Agents

3. CEST Probes: Multiple Labeling Frequencies

3.1. Diamagnetic CEST probes

3.2. Paramagnetic CEST probes

3.3. Nanoparticle-based CEST probes

4. 19F Probes: Hot-Spot Imaging

4.1. 19F-containing metal complexes

4.2. 19F-containing nanoemulsions

5. Hyperpolarized Imaging Probes

5.1. Dynamic nuclear polarization

5.2. Parahydrogen-induced polarization

5.3. Spin exchange optical pumping

References

Chapter Ten: Clinical Translation of Molecular Imaging Agents Used in PET Studies of Cancer

1. Introduction

2. FDG-Lessons Learnt

3. Stages to Development of a New Radiotracer

4. Translating Deregulated Nature-Identical Biochemicals

4.1. Choline metabolism

4.2. Fatty acid metabolism

4.3. Amino acid metabolism

5. Translating Cell Surface and Intracellular Receptors as Predictive Biomarkers

5.1. Epidermal growth factor receptor in lung cancer

5.2. HER2 in breast cancer

5.3. ER signaling in breast cancer

5.4. PSMA in prostate cancer

6. Translating Probes for Visualization of Life and Death Signals in the Cell

6.1. Proliferation

6.2. Apoptosis

7. Translating Tools to Assess Host-Tumor Microenvironment Interactions

7.1. Angiogenesis

7.2. Hypoxia imaging

8. Translating Labeled Drugs and Drug Analogs

9. Conclusion

Acknowledgments

References

Index

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