Biomedical imaging : the chemistry of labels, probes, and contrast agents

553 Pages·2012·24.64 MB·English

by  Martin Braddock

RSC Drug Discovery
Edited by Martin Braddock
Biomedical Imaging
The Chemistry of Labels, Probes and Contrast Agents
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Biomedical Imaging
The Chemistry of Labels, Probes and Contrast Agents
RSC Drug Discovery Series
Editor-in-Chief:
Professor David Thurston, London School of Pharmacy, UK
Series Editors:
Dr David Fox, Pfizer Global Research and Development, Sandwich, UK
Professor Salvatore Guccione, University of Catania, Italy
Professor Ana Martinez, Instituto de Quimica Medica-CSIC, Spain
Dr David Rotella, Montclair State University, USA
Advisor to the Board:
Professor Robin Ganellin, University College London, UK
Titles in the Series:
1:Metabolism,PharmacokineticsandToxicityofFunctionalGroups:Impact
of Chemical Building Blocks on ADMET
2:Emerging Drugs and Targets for Alzheimer’s Disease; Volume 1: Beta-
Amyloid, Tau Protein and Glucose Metabolism
3:EmergingDrugsandTargetsforAlzheimer’sDisease;Volume2:Neuronal
Plasticity, Neuronal Protection and Other Miscellaneous Strategies
4: Accounts in Drug Discovery: Case Studies in Medicinal Chemistry
5: New Frontiers in Chemical Biology: Enabling Drug Discovery
6: Animal Models for Neurodegenerative Disease
7: Neurodegeneration: Metallostasis and Proteostasis
8: G Protein-Coupled Receptors: From Structure to Function
9: Pharmaceutical Process Development: Current Chemical and Engineering
Challenges
10: Extracellular and Intracellular Signaling
11: New Synthetic Technologies in Medicinal Chemistry
12: New Horizons in Predictive Toxicology: Current Status and Application
13: Drug Design Strategies: Quantitative Approaches
14: Neglected Diseases and Drug Discovery
15:BiomedicalImaging:TheChemistryofLabels,ProbesandContrastAgents
How to obtain future titles on publication:
A standing order plan is available for this series. A standing order will bring
delivery of each new volume immediately on publication.
For further information please contact:
BookSalesDepartment,RoyalSocietyofChemistry,ThomasGrahamHouse,
Science Park, Milton Road, Cambridge, CB4 0WF, UK
Telephone:[phone],Fax:[phone],Email:[email protected]
Visit our website at http://www.rsc.org/Shop/Books/
Biomedical Imaging
The Chemistry of Labels, Probes and
Contrast Agents
Edited by
Martin Braddock
AstraZeneca, Loughborough, UK
RSCDrugDiscoverySeriesNo.15
ISBN: 978-1-84973-014-3
ISSN: 2041-3203
AcataloguerecordforthisbookisavailablefromtheBritishLibrary
rRoyalSocietyofChemistry2012
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Preface
The concept of medical imaging is one of the cornerstones of modern medi-
cine. Although its origins can be found in 19th century photography, the field
only properly emerged in 1895 following W. C. Ro¨ntgen’s discovery of X-
rays. Since then, insights from across physics and chemistry have devised
many more modalities, such as magnetic resonance imaging (MRI), optical
imaging (including fluorescence), X-ray imaging (including X-ray Computed
Tomography, CT), gamma imaging (including Single Photon Emission Com-
puted Tomography, SPECT), positron emission tomography (PET) and
ultrasound techniques.
In this exemplary new book a distinguished group of experts from both
industry and academia present a comprehensive review on how medical ima-
gingisbeingusedinscreening,diagnosis,patientmanagement,clinicalresearch
and to assist in the development of new therapeutic drugs.
Biomedical Imaging: The Chemistry of Labels, Probes and Contrast Agents
begins with a comprehensive introduction to endogenous and exogenous
contrastinmedicalimaging.Thebookisthenbrokendownintofoursections.
Section one presents a review of some of the more important advances in
recent years such as the development of radiotracers and radio-
pharmaceuticalsasbiomedicalimagingtools,recentdevelopmentsinimaging
agentsforselectedbraintargetsthatareofclinicalrelevanceinpsychiatryand
neurology and of pharmacological interest in drug discovery and develop-
ment and the synthesis of radiopharmaceuticals for application in SPECT
imaging. Section two focuses on the design and synthesis of contrast agents,
MRI and X-ray modalities. Topics covered include the synthesis and appli-
cationsofMRIcontrastagents,syntheticmethodsusedforthepreparationof
DTPA and DOTA derivative ligands, MRI contrast agents based on metal-
lofullerenes, applications of MRI in radiotherapy treatment and the use of
autoradiography in the pharmaceutical discovery and development of
RSCDrugDiscoverySeriesNo.15
BiomedicalImaging:TheChemistryofLabels,ProbesandContrastAgents
EditedbyMartinBraddock
rRoyalSocietyofChemistry2012
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
v
vi Preface
xenobiotics.Sectionthreeconcentratesonopticalimagingtechniquesandthe
value of fluorescence optical imaging in pharmacological research and drug
development.Therearealsochaptersonfluorescencelifetimeimagingapplied
to microviscosity mapping and fluorescence modification studies in cells and
thedesignanduseofcontrastagentsforultrasoundimaging.Thefinalsection
focuses on physical techniques and application, with a review of recent
advances in brain imaging that provide opportunities to develop biomarkers
for diseases of the central nervous system (CNS) and current progress and
futureprospectsofusingMRItoassistinthedrugdiscoveryanddevelopment
process.Thefinalchapterbringsthebooktoaclosepeeringintothefutureof
MRI contrast agents.
This book will be essential reading for medicinal and physical scientists
working in both industry and academia in the fields of chemistry, physics,
radiology, biochemistry and pharmaceutical sciences.
Contents
Chapter1 MedicalImaging:OverviewandtheImportanceofContrast 1
John C Waterton
1.1 Introduction 1
1.2 Medical Imaging Modalities 4
1.2.1 Some General Ideas 4
1.2.2 Imaging and the Electromagnetic Spectrum 5
1.2.3 Radio Frequencies and Below 6
1.2.4 Magnetic Resonance 6
1.2.5 Microwaves 10
1.2.6 Optical Imaging 10
1.2.7 Ultraviolet 11
1.2.8 X-Ray 12
1.2.9 Gamma Rays and Nuclear Medicine 13
1.2.10 Single Photon Emission Computed
Tomography 13
1.2.11 Positron Emission Tomography 14
1.2.12 Ultrasound 15
1.2.13 Multimodal Techniques 16
1.3 How is Medical Imaging Used? 16
1.3.1 Prognostic or Diagnostic Biomarkers 17
1.3.2 Predictive Biomarkers or Companion
Diagnostics 17
1.3.3 Monitoring Biomarkers 17
1.3.4 Response Biomarkers 18
1.4 Regulatory and Cost Issues 18
1.5 Conclusion 19
References 20
RSCDrugDiscoverySeriesNo.15
BiomedicalImaging:TheChemistryofLabels,ProbesandContrastAgents
EditedbyMartinBraddock
rRoyalSocietyofChemistry2012
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
vii
viii Contents
Chapter 2 Biomedical Imaging: Advances in Radiotracer and
Radiopharmaceutical Chemistry 21
Robert N Hanson
2.1 Background 21
2.1.1 Factors in Radiopharmaceutical Design and
Synthesis 22
2.2 Recent Examples of Integrated Radiotracer and
Radiopharmaceutical Development 25
2.2.1 b-Amyloid Targeted Agents for Imaging in
Alzheimer’s Disease 27
2.2.2 PSMA Targeting for Imaging Prostate Cancer 30
2.2.3 Integrin Receptor Targeted Agents for
Imaging Cancer 35
2.3 Conclusions 38
Acknowledgments 39
References 39
Chapter 3 Recent Developments in PET and SPECT Radioligands
for CNS Imaging 49
DavidAlagille,RonaldM.BaldwinandGillesD.Tamagnan
3.1 Introduction 49
3.2 Amyloid Plaque 50
3.2.1 2-(4-([11C]Methyl amino)phenyl)benzo[d]
thiazol-6-ol ([11C]PIB) 51
3.2.2 2-(1-(6-((2-[18F]fluoroethyl)(methyl)amino)-2-
naphthyl)ethylidene)malononitrile([18F]FDDNP) 54
3.2.3 6-[123I]iodo-2-(4’-dimethylamino)phenyl-
imidazo[1,2-a]pyridine ([123I]IMPY) 55
3.2.4 2-(2-(2-Dimethylaminothiazol-5-yl)ethenyl)-
6-(2([18F]fluoro)ethoxy)benzoxazole
([18F]BF227) and 2-(2-(2-N-methyl-N-
[11C]methyl-aminothiazol-5-yl)ethenyl)-6-
(2(fluoro)ethoxy)benzoxazole ([11C]BF-227) 56
3.2.5 trans-4-(N-Methylamino)-4’-(2-(2-(2-[18F]
fluoroethoxy)ethoxy)stilbene ([18F]BAY94–
9172 or [18F]florbetaben) 57
3.3 Metabotropic Glutamate Receptors 58
3.3.1 mGluR1 58
3.3.2 Metabotropic Glutamate Type 5 (mGluR5)
Receptor 60
3.4 Monoamine Transporter Targets 64
3.4.1 Dopamine Transporter (DAT) 64
3.4.2 Norepinephrine Transporter (NET) 71
3.4.3 Serotonin Transporter (SERT or 5-HTT) 75
Contents ix
3.5 Vesicular Monoamine Transporter Type 2
(VMAT2) 80
3.5.1 [11C]-Tetrabenazine ([11C]TBZ) 81
3.5.2 [11C]-Methoxytetrabenazine
([11C]MTBZ) 82
3.5.3 [125I]-Iodovinyltetrabenazine
([123I]IV-TBZOH) 83
3.5.4 [11C]Dihydrotetrabenazine ([11C]TBZOH) 83
3.5.5 Fluoroalkyl dihydrotetrabenazine
([18F]FE-DTBZ and [18F]FP-DTBZ) 85
3.6 Post-Synaptic Dopamine Receptor D3 (D3r) 85
3.6.1 [11C](þ)-4-Propyl-3,4,4a,5,6,10b-
hexahydro-2H-naphto-[1,2-b][1,4]oxazin-
9-ol ([11C](þ)-PHNO) (Figure 3.8) 86
3.7 Post-Synaptic Serotonin Receptor Targets 88
3.7.1 Serotonin Receptor Subtype 4 (5-HT4) 89
3.7.2 Serotonin Receptor Subtype 6 (5-HT6) 90
3.8 Peripheral Benzodiazepine Receptor, PBR
(Translocator Protein 18kD, TSPO) 91
3.8.1 1-(2-Chlorophenyl)-N-[11C]methyl-N-
(1-methylpropyl)-3-isoquinoline
carboxamide ([11C]PK11195) 93
3.8.2 N-[18F]Fluoroacetyl-N-(2,5-dimethoxybenzyl)-
2-phenoxyaniline ([18F]PBR06) and N-acetyl-
N-(2-[11C]methoxybenzyl)-2-phenoxy-5-
pyridinamine ([11C]PBR28) 94
3.8.3 N-Acetyl-N-(2-[11C]methoxybenzyl)-2-
phenoxy-5-pyridinamide ([11C]PBR06) 95
3.9 Phosphodiesterase Inhibitors 95
3.9.1 PDE4 97
3.9.2 PDE10 98
3.10 Adenosine Receptor A1 and A2A 99
3.10.1 8-Dicyclopropylmethyl-1-[11C]methyl-3-
propylxantine ([11C]MPDX) 100
3.10.2 8-cyclopentyl-3-[(E)-3-iodoprop-2-en-1-yl]-
1-propylxanthine ([131I]CPIPX) 101
3.10.3 8-Cyclopentyl-3-(3-[18F]fluoropropyl)-1-
propylxanthine ([18F]CPFPX) 102
3.10.4 [11C]2-(1-Methyl-4-piperidinyl)-6-(2-
phenylpyrazolo[1,5-a]pyridine-3-yl)-
3(2H)-pyridazinone ([11C]FR194921) 103
3.10.5 (E)-8-(3,4-Dimethoxystyryl)-1,3-dipropyl-7-
[11C]methylxanthine ([11C]KF17837) 104
3.10.6 [7-Methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-
1,3,7-trimethylxanthine ([11C]KF18446
or [11C]TMSX) 104