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Imaging of Hypoxia : Tracer Developments - Hans-Jurgen Machulla

Imaging of Hypoxia

Tracer Developments

By: Hans-Jurgen Machulla (Editor)

Hardcover Published: 31st January 1999
ISBN: 9780792355298
Number Of Pages: 180

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Hypoxia, i.e. insufficient availability of oxygen within the tissue, is a more serious problem than realized in clinical routine work, although a large variety of theoretical and experimental data give clearly proven indications. During incidences and progress of many types of diseases hypoxia may enhance development and progress of the disease and, furthermore, decrease chances of efficient treatment of, e.g., tumors. Hypoxic tumor cells are up to three times more resistant towards radiation therapy than normoxic cells. With a diagnostic tool such as provided by hypoxia tracers suitable for PET and SPECT imaging, the particular tissue situation becomes detectable and, thus, treatable. Although the clinical importance of hypoxia imaging is obviously great, to date neither the clinical nor the scientific community at an international level has focused many research activities on the hypoxia problem. As the result of a workshop held by the Section for Radiopharmacy in TA1/4bingen, this book collects observations and findings in order to stimulate the on-going research resulting in important clinical applications. Hypoxia imaging is needed in areas of cardiology, neurology and oncology. Additional applications are to be expected in the field of diabetes, infections and organ transplantation. Therefore, the book addresses those who are basically involved in research in radiochemistry and radiopharmacy as well as those dealing with all biological aspects and facing direct clinical applications.

`Overall, this text provides a summary of the status of radionuclide imaging of hypoxia. The material is clearly prestented, well referenced and authoritative. The text is concise, and should serve as a reference for investigators interested in pursuing work in this field.' European Journal of Nuclear Medicine 28:5,(2001)

Prefacep. ix
List of Contributorsp. xi
Color Figuresp. xiii
Hypoxia: An Introduction
Definitions of Hypoxiap. 1
Predictive Assays for Tissue Hypoxiap. 2
The Design of Predictive Assaysp. 2
Predictive Assays based on the Measurement of Tissue Hypoxiap. 3
Hypoxia in Selected Pathologiesp. 4
Oncologyp. 4
Cardiovascular Diseasep. 6
Cerebrovascular Diseasep. 7
Diabetesp. 10
Infectionp. 10
Wound Healing and Organ Transplantationp. 11
Joint Hypoxiap. 11
Other Cutaneous and Mucosal Pathologiesp. 12
Aspects of Cellular Metabolism in Hypoxiap. 13
Radiotherapy and Hypoxiap. 14
Radiobiological Hypoxiap. 14
Radiosensitizersp. 15
Hypoxic Binding of 2-Nitroimidazolesp. 15
Further Readingp. 16
The Biology of Technetium Based Hypoxic Tissue Localising Compounds
Introductionp. 19
Oxygen concentrations in tissuesp. 20
Oxygen levels required for trapping of nitroimidazolesp. 21
Individual cellsp. 22
Isolated perfused heartsp. 23
Myocardium in vivop. 26
Conclusionsp. 27
Flow levels required for trappingp. 28
Myocardiump. 28
Brainp. 30
Conclusionsp. 30
Trapping mechanismsp. 31
Imaging/Kineticsp. 34
Brainp. 34
Heartp. 34
Tumoursp. 35
Comparison to other metabolic imaging agentsp. 36
Toxicityp. 38
Toxicity of therapeutic nitroimidazolesp. 38
Pharmacokinetics of therapeutic nitroimidazolesp. 40
Assessment of toxicity of diagnostic dosesp. 41
Basic Chemistry of 2-Nitroimidazoles (Azomycin Derivates)
Introductionp. 47
Imidazolep. 48
2-Nitroimidazole (Azomycin)p. 48
Preparation of 2-nitroimidazolep. 49
Chemical properties of 2-nitroimidazolep. 50
Reactivity of 2-nitroimidazolep. 50
5-Substituted 2-nitroimidazolesp. 54
2-Nitroimidazole nucleosides and analogsp. 54
Azomycin ribosidep. 54
Azomycin nucleosidesp. 55
Azomycin nucleoside analogsp. 55
Molecular Design Approaches of Hypoxia Tracers
Introductionp. 61
Modelling of Ligand Protein Interaction Complexesp. 62
The QSAR Approachp. 65
Threedimensional QSAR and Pseudoreceptorsp. 66
Material and Methodsp. 67
Resultsp. 70
Molecular electrostatic potentialsp. 70
Formation of Radicalsp. 71
Outlookp. 73
Syntheses of PET-Tracers for the Determination of Hypoxia
Syntheses of [[superscript 18]F]FMISOp. 75
Synthesis of alternative [[superscript 18]F]-labelled agents for hypoxia imagingp. 80
Summary and future directionsp. 81
Quantifying Hypoxia with Radiolabeled Fluoromisonidazole: Pre-Clinical and Clinical Studies
Introductionp. 85
Rational approachp. 85
Properties of fluromisonidazole that make it a useful tracerp. 87
Development of FMISO as a PET tracer: From cells in vitro to patient imagingp. 87
Cell Monolayers and Spheroids in Culturep. 88
Cell monolayer studiesp. 88
Spheroid Studiesp. 89
Isolated myocyte studiesp. 90
Studies in Animalsp. 90
Micep. 90
Ratsp. 95
Tumor studies in dogsp. 98
Heart studies in dogsp. 100
Patient Studiesp. 103
Tumor studiesp. 103
Heart studiesp. 111
Summary and Conclusionsp. 113
Detection of Liver Hypoxia by [[superscript 18]F]Fluoromisonidazole and Application in Liver Transplant Disorders
Introductionp. 119
Liver tissue hypoxia in transplant dysfunctionsp. 119
Hypoxia and rejectionp. 119
Hypoxia and immunosuppressive therapyp. 120
Differential diagnoses in transplant dysfunctionsp. 121
Material and methodsp. 121
Resultsp. 122
Discussionp. 125
Conclusionp. 126
The Evaluation of Hypoxia in Diabetes
Introductionp. 129
Microangiopathy in Diabetic Patientsp. 130
Biochemical Processes and Pathwaysp. 130
Structural and Functional Changesp. 131
The Diabetic Footp. 132
Assessment of Hypoxia in the Diabetic Footp. 133
Imaging and Nuclear Medicine Methods in the Evaluation of Tissue Hypoxia in Diabetesp. 138
Non-Radionuclide Imagingp. 138
Radiopharmaceuticals and Diabetic Hypoxiap. 139
Conclusionsp. 145
Radiohalogenated Nitroimidazoles for Single-photon Scintigraphic Imaging of Hypoxic Tissues
Rational Design of Hypoxia-specific Radiotracersp. 155
The 'oxygen effect' and chemical radiosensitizersp. 155
Nitroimidazole radiosensitizer designp. 155
Metabolism of 2-nitroimidazolesp. 157
Radiohalogenated Imidazole-based Radiopharmaceuticals for SPECT and Planar Imagingp. 158
Hypoxia tracers labelled with [superscript 82]Brp. 158
Radioiodinated 4(5)-nitroimidazole analoguesp. 159
Radioiodinated 2-Nitroimidazolesp. 160
Azomycin Nucleosidesp. 163
Discussionp. 169
Table of Contents provided by Syndetics. All Rights Reserved.

ISBN: 9780792355298
ISBN-10: 0792355296
Series: DEVELOPMENTS IN NUCLEAR MEDICINE
Audience: Professional
Format: Hardcover
Language: English
Number Of Pages: 180
Published: 31st January 1999
Publisher: Springer
Country of Publication: NL
Dimensions (cm): 24.13 x 16.51  x 1.27
Weight (kg): 0.46