Since their clinical use initiation in the 1970's, Fluorine-18 (F-18) radiopharmaceuticals continue to play an important role in nuclear medicine. It is therefore essential to make available broad information on practical production routes and optimal quality control for F- 18 tracers, to achieve the best possible products in high quantity and quality for clinical applications while fulfilling all regulatory requirements. This publication describes the chemical and biological properties of F-18 radiopharmaceuticals. This includes aspects relating to F-18 target production and radiofluorination methods, with focus on the applied techniques. The publication presents a disease oriented approach, describing F-18 radiopharmaceuticals, ranging from the physiological/biological aspects to dedicated radiopharmaceutical development approaches and provides readers with clear guidelines and methods for the production of F-18 radiopharmaceuticals.

The thoroughly updated new edition of the authoritative reference in Radiopharmaceutical Sciences The second edition of Handbook of Radiopharmaceuticals is a comprehensive review of the field, presenting up-to-date coverage of central topics such as radionuclide production, synthetic methodology, radiopharmaceutical development and regulations, and a wide range of practical applications. A valuable reference work for those new to the Radiopharmaceutical Sciences and experienced professionals alike, this volume explores the latest concepts and issues involving both targeted diagnostic and therapeutic radiopharmaceuticals. Contributions from a team of experts from across sub-disciplines provide readers with an immersive examination of radiochemistry, nuclear medicine, molecular imaging, and more. Since the first edition of the Handbook was published, Nuclear Medicine and Radiopharmaceutical Sciences have undergone major changes. New radiopharmaceuticals for diagnosis and therapy have been approved by the FDA, the number of clinical PET and SPECT scans have increased significantly, and advances in Artificial Intelligence have dramatically improved research techniques. This fully revised edition reflects the current state of the field and features substantially updated and expanded content. New chapters cover topics including current Good Manufacturing Practice (cGMP), regulatory oversight, novel approaches to quality control—ensuring that readers are informed of the exciting developments of recent years. This important resource: Features extensive new and revised content throughout Covers key areas of application for diagnosis and therapy in oncology, neurology, and cardiology Emphasizes the multidisciplinary nature of Radiopharmaceutical Sciences Discusses how drug companies are using modern radiopharmaceutical imaging techniques to support drug discovery Examines current and emerging applications of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) Edited by recognized experts in radiochemistry and PET imaging, Handbook of Radiopharmaceuticals: Radiochemistry and Applications, 2 nd Edition is an indispensable reference for post-doctoral fellows, research scientists, and professionals in the pharmaceutical industry, and for academics, graduate students, and newcomers in the field of radiopharmaceuticals.

Radiopharmaceuticals and Other Compounds Labelled with Short-Lived Radionuclides covers through both review and contributed articles the potential applications and developments in labeling with short-lived radionuclides whose use is restricted to institutions with accelerators. The book discusses the current and potential use of generator-produced radionuclides as well as other short-lived radionuclides, and the problems of quality control of such labeled compounds. The book is useful to nuclear medicine physicians.

This book describes methods and procedures for preparing PET radiopharmaceuticals, and highlights new methods for conducting radiochemical reactions with carbon-11 (C11) and fluorine-18 (F18), which are two of the most commonly used radionuclides in positron emission tomography (PET) imaging. • Provides reliable methods for radiochemical syntheses and reactions, including all essential information to duplicate the procedure • Eliminates the time-consuming process of searching journal articles and extracting pertinent details from lengthy experimental sections or supporting information • Focuses on an emerging and important area for pharmaceutical and medical applications • Encompasses technical, regulatory, and application aspects • Includes solid-phase radiochemistry, transition-metal catalyzed radiochemistry, microfluidics, click chemistry, green radiochemistry and new strategies for radiopharmaceutical quality control

Marking the 200th National Meeting of the American Chemical Society, The Division of Nuclear Chemistry and Technology hosted a group of about 90 scientists from 15 different countries to discuss the new trends in radiopharmaceutical synthesis, quality assurance and regulatory control. This event took place in Washington, D.C. on August 27-30, 1990. When I first suggested the idea for this symposium, a group of scientists who pioneered the proposed topics offered their help to organize and run such a big task with me. Their names are listed here in appreciation. Thomas E. Boothe Cyclotron Facility, Mt. Sinai Medical Center, Miami Beach, Florida, USA Robert F. Dannals Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Anthony L. Feliu Julich Nuclear Research Center, Julich, Germany Joanna S. Fowler Chemistry Department, Brookhaven National Laboratory, Upton, New York, USA George W. Kabalka Department of Chemistry, University of Tennessee, Knoxville, Tennessee, USA Hank F. Kung Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA James F. Lamb Imagents, Inc., Houston, Texas, USA Harold A. O'Brien, Jr. Los Alamos National Laboratory, Los Alamos, New Mexico, USA Joseph R. Peterson Dept. of Chemistry, University of Tennessee, Knoxville, Tennessee, USA Hernan Vera Ruiz International Atomic Energy Agency, Vienna, Austria Roy S. Tilbury University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA In addition, a number of distinguished colleagues have participated in the process of reviewing the manuscripts presented in this volume. Their effort is sincerely acknowledged.

Positron emission tomography (PET) is a powerful medical diagnostics and research tool that uses radiolabeled molecules (tracers) to image biological processes in vivo. By administering only nanomolar quantities of the tracers, PET scans enable non-invasive assessment of normal biological processes in cells and their failure in disease to aid in medical diagnostics, staging of disease severity and monitoring treatment response. Short-lived radioisotopes used in the synthesis of diagnostic PET tracers necessitate that the tracer production is carried out shortly before imaging. Each production is a multistep process involving acquisition of the radioisotope, radiochemical synthesis and quality control. Radiochemical synthesis is further broken down into radiochemical reaction to link the radioisotope with a ligand, purification and formulation to obtain pure injection-ready product.Despite impressive sensitivity and accuracy of PET in medical diagnostics, access to the wide variety of short-lived radioactive tracers is hindered due to a high cost of their preparation. The overall preparation cost covers: (i) radiosynthesis units and various consumables, (ii) large shielded fume hoods (hot-cells), (iii) reagents and radioisotope, (iv) labor and safety. A typical centralized production of PET tracers in large radiochemistry facilities alleviates the high cost per production by splitting of the large batches and shipping those to multiple users, which is only possible for tracers in high demand such as [18F]fluorodeoxyglucose ([18F]FDG). Newly introduced dose-on-demand concept proposes convenient production of any tracer of interest directly at the imaging location, leading to a decentralized approach. While setting up dedicated conventional radiosynthesis modules for this purpose is unrealistic due to the high cost and large footprint, microfluidic approaches provide a path for a miniaturized, economical tracer production. Our lab among others has been extensively working on the radiosynthesis miniaturization using droplet microfluidic methods. Microfluidics offers potential of cost reduction in almost all aspects of radiosynthesis. (i) The synthesizer cost can be reduced as a result of reduced system size, complexity and consumables cost, (ii) the compact units can be self-shielded not requiring use of hot-cells, (iii) the reagent and radioisotope consumption per synthesis is orders of magnitude less, (iv) the faster synthesis times and small-scale production levels reduce labor burden and improve safety. Additionally, in fluorine-18 radiochemistry, the conventional synthesizers must use high starting radioactivity to ensure good molar activity (radioactivity per moles of the substance) of the final product. Previously, our group has developed automated droplet reactors based on electrowetting on dielectric (EWOD) technology. However, those devices had limitations due to high cost and complexity of fabrication. More recently, we introduced low-cost disposable silicon chips which serve as a reactor within an ultra-compact automated radiosynthesizer unit, comparable in size to a 12 oz. coffee cup. The major part of this dissertation was adapting various conventional fluorine-18-labeling synthesis methods to a droplet format to demonstrate the versatility of this radiosynthesis approach. For a number of tracers, we describe synthesis miniaturization process and demonstrate that the droplet syntheses exhibit higher yields and improved synthesis times in comparison to the conventional methods. All syntheses feature orders-of-magnitude reduction in reagent consumption and are able to achieve high molar activity even when lower starting amounts of the radioisotope are used. As a result, low cost per production can be achieved and such methods are readily useable for research in particular that involves small animal PET imaging. Importantly, we further demonstrate that these syntheses are scalable, and that production of a few human doses is feasible. For validation, we also perform full clinical quality control on these tracer batches. These results suggest that in the future it would be possible to introduce this technology in a clinical setting as well for an easy access to a wide variety of PET tracers. From the radiochemistry standpoint, microfluidic fluorine-18 radiolabeling has been shown to work for different type of ligands. Apart from small molecule radiolabeling, peptide labeling routes via droplet radiochemistry are also shown. In this work we feature isotopic exchange (IEX) fluorination that has a benefit of simplified purification but is challenging on conventional scale due to inherently lower molar activity in this type of reactions. We demonstrate that the droplet approach with its small volumes allows one to perform IEX synthesis of trifluoroborate-based peptides and prosthetic groups with high yields and molar activities. This dissertation presents reliable methods for fluorine-18-labeled radiopharmaceutical production on demand, in a time- and cost-efficient manner for diverse PET tracers. While with the current progress, these methods can be readily applied for research purposes including pre-clinical PET imaging, and future work will focus on improvements and optimization of the droplet microfluidic technologies to advance these methods to the clinical PET.

Radiochemical methodology constitutes the most important base for the successful functioning of a PET group in the routine production and development of radiopharmaceuticals. Of the several hundred products which have been labelled with positron emitters during the past two decades about 35 are presently considered to be of major interest. The time for a state-of-the-art review is right, since this field has advanced over the past fifteen years to reach a level where guidelines can now be suggested. Chapters of this book deal with each of the main methodological aspects of the chemistry needed to develop an effective radiopharmaceutical, namely radionuclide production, automation and metabolite analysis. A further chapter on QA/QC is written by a broadly-based expert group and is meant to provide a guideline and a base for future monographs and regulations on major PET radiopharmaceuticals of today. This book will help the increasing numbers of scientists who are now entering the field of PET to appreciate the methodological aspects that are normally addressed by chemists in relation to PET radiopharmaceuticals; it provides many useful practical guidelines and will promote early success in their own endeavours, since these will often necessarily begin by establishing chemical methodology of the kind discussed here.

This publication provides practical information for planning and operating a fluorodeoxyglucose (FDG) production facility, including design and implementation of the laboratories, facility layout, equipment, personnel, and quality assessment of FDG. Information useful for assessing the resource requirements, planning and aspects necessary for compliance with the applicable national regulatory requirements for manufacturing of radio-pharmaceuticals is also included.

A comprehensive, authoritative and up-to-date reference for the newcomer to radiopharmaceuticals and those already in the field. Radiopharmaceuticals are used to detect and characterise disease processes, or normal biological function, in living cells, animals or humans. Used as tracer molecules, they map the distribution, uptake and metabolism of the molecule in clinical studies, basic research or applied research. The area of radiopharmaceuticals is expanding rapidly. The number of PET centers in the world is increasing at 20% per year, and many drug companies are utilising PET and other forms of radiopharmaceutical imaging to evaluate products. * Readers will find coverage on a number of important topics such as radionuclide production, PET and drug development, and regulations * Explains how to use radiopharmaceuticals for the diagnosis and therapy of cancer and other diseases * The editors and a majority of the contributors are from the United States