With the increasing interest in the experimental and clinical application of molecular imaging many institutions create research groups or interdisciplinary centers focussing on the complex development process of this new methodology. The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is beeing addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation.

It is the mark of an instructed mind to rest satisfied with the degree of precision which the nature of the subject admits, and not to seek exactness where only an approximation of the truth is possible. Aristotle With the development of imaging techniques, the in vivo study of human anatomy and physiology has become possible with increasing "approximation of the truth. " Advances have been made not only in data acquisition, but also in processing as well as visualization of functional and morphological data. Following the successful application of planar two-dimensional imaging approaches, more recently three-dimensional data acquisition and correspond ing tomographic image reconstruction has become possible. With the rapid growth of computer support, advanced processing allows for user-friendly interaction with complex data sets. Classical x-ray imaging techniques have matured to excellent spatial resolution and contrast, which provide specific delineation of anatomical changes occurring in cardiovascular disease. In parallel, the use of tracer principles supported the successful introduction of nuclear medicine procedures for the functional characterization of physiology and pathophysiology. The application of such techniques were initially limited by relatively poor spatial resolution, but excelled in high sensitivity 30 years, scintigraphic imaging emerged from and specificity. In the last rectilinear scanning to planar gamma camera imaging and single-photon xvi Preface emISSIOn tomography (SPECT). Based on these advances and the experi mental success of autoradiography, the potential of scintigraphy as a clinical and research tool has been well appreciated.

This book explains in detail the potential value of the hybrid modalities, SPECT-CT and PET-CT, in the imaging of cardiac innervation in a wide range of conditions and diseases, including ischemic heart disease, diabetes mellitus, heart failure, amyloidosis, heart transplantation, and ventricular arrhythmias. Imaging of the brain-heart axis in neurodegenerative disease and stress and of cardiotoxicity is also discussed. The roles of the various available tracers are fully considered, and individual chapters address radiopharmaceutical development under GMP, imaging physics, and kinetic modeling software. Highly relevant background information is included on the autonomic nervous system of the heart and its pathophysiology, and in addition future perspectives are discussed. Awareness of the importance of autonomic innervation of the heart for the optimal management of cardiac patients is growing, and there is an evident need for objective measurement techniques or imaging modalities. In this context, Autonomic Innervation of the Heart will be of wide interest to clinicians, researchers, and industry.

Because of the current progress in molecular medicine (genomics, proteomics), a plethora of new and often human-specific targets are being identified. These targets often play a significant role in the pathogenesis of diseases, and identifying them offers the potential for early diagnosis and intervention. An early in vivo validation of specific ligands binding to these targets in humans is needed to as- sess their potential for targeted imaging and radiotherapy. Further- VI Preface more, such validation studies may allow for a better understanding of the molecular processes underlying phannacologic activity and therefore for a more successful development of phannaceuticals in general. The purpose of the Ernst Schering Research Foundation (ESRF) Workshop 48 was to provide a forum for an open exchange on the state of the art in the early development of such radiophanna- ceuticals. Experts from academia, industry, and regulatory authori- ties were invited to give presentations on aspects covering the identi- fication of targets, preclinical studies on the safety of ligands, as well as their validation in human clinical trials. It was our intention to cover both the opportunities and the challenges that scientists in this field are facing. Radiopharmaceuticals are uniquely suitable for the above-men- tioned target validation studies.

With the increasing interest in the experimental and clinical application of molecular imaging many institutions create research groups or interdisciplinary centers focussing on the complex development process of this new methodology. The aim for this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is being addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation.

It is the mark of an instructed mind to rest satisfied with the degree of precision which the nature of the subject admits, and not to seek exactness where only an approximation of the truth is possible. Aristotle With the development of imaging techniques, the in vivo study of human anatomy and physiology has become possible with increasing "approximation of the truth. " Advances have been made not only in data acquisition, but also in processing as well as visualization of functional and morphological data. Following the successful application of planar two-dimensional imaging approaches, more recently three-dimensional data acquisition and correspond ing tomographic image reconstruction has become possible. With the rapid growth of computer support, advanced processing allows for user-friendly interaction with complex data sets. Classical x-ray imaging techniques have matured to excellent spatial resolution and contrast, which provide specific delineation of anatomical changes occurring in cardiovascular disease. In parallel, the use of tracer principles supported the successful introduction of nuclear medicine procedures for the functional characterization of physiology and pathophysiology. The application of such techniques were initially limited by relatively poor spatial resolution, but excelled in high sensitivity 30 years, scintigraphic imaging emerged from and specificity. In the last rectilinear scanning to planar gamma camera imaging and single-photon xvi Preface emISSIOn tomography (SPECT). Based on these advances and the experi mental success of autoradiography, the potential of scintigraphy as a clinical and research tool has been well appreciated."

Because of the current progress in molecular medicine (genomics, proteomics), a plethora of new and often human-specific targets are being identified. These targets often play a significant role in the pathogenesis of diseases, and identifying them offers the potential for early diagnosis and intervention. An early in vivo validation of specific ligands binding to these targets in humans is needed to as- sess their potential for targeted imaging and radiotherapy. Further- VI Preface more, such validation studies may allow for a better understanding of the molecular processes underlying phannacologic activity and therefore for a more successful development of phannaceuticals in general. The purpose of the Ernst Schering Research Foundation (ESRF) Workshop 48 was to provide a forum for an open exchange on the state of the art in the early development of such radiophanna- ceuticals. Experts from academia, industry, and regulatory authori- ties were invited to give presentations on aspects covering the identi- fication of targets, preclinical studies on the safety of ligands, as well as their validation in human clinical trials. It was our intention to cover both the opportunities and the challenges that scientists in this field are facing. Radiopharmaceuticals are uniquely suitable for the above-men- tioned target validation studies.