Handbook of Nuclear Medicine and Molecular Imaging for Physicists

Radiopharmaceuticals and Clinical Applications, Volume III

Michael Ljungberg

• Publisher: CRC Press
• Year: 2022
• ISBN:
  9780429952098
• Edition: 1
• Topic: Medicine
• Subtopic: Radiology, Radiotherapy & Nuclear Medicine

This state-of-the-art handbook, the third and final in a series that provides medical physicists with a comprehensive overview into the field of nuclear medicine, focuses on highlighting the production and application of radiopharmaceuticals. With this, the book also describes the chemical composition of these compounds, as well as some of the main clinical applications where radiopharmaceuticals may be used.

Following an introduction to the field of radiopharmacy, three chapters in this book are dedicated towards in-depth descriptions of common radionuclides and radiopharmaceuticals used during diagnostic studies utilizing planar/Single Photon Emission Computed Tomography (SPECT) imaging, in addition to during Positron Emission Tomography (PET) imaging, and, finally, radiotherapy. These chapters are followed by those describing procedures relating to quality control and manufacturing (good manufacturing practices) also encompassing aspects such as environmental compliance. Furthermore, this volume illustrates how facilities handling these chemicals should be designed to comply with set regulations.

Like many pharmaceuticals, the development of radiopharmaceuticals relies heavily on the use of mouse models. Thus, the translation of radiopharmaceuticals (i.e., the process undertaken to assure that the functionality and safety of a newly developed drug is maintained also in a human context), is covered in a later chapter. This is followed by a chapter emphasising the importance of safe waste disposal and how to assure that these procedures meet the requirements set for the disposal of hazardous waste.

Several chapters have also been dedicated towards describing various medical procedures utilizing clinical nuclear medicine as a tool for diagnostics and therapeutics. As physicists may be involved in clinical trials, a chapter describing the procedures and regulations associated with these types of studies is included. This is followed by a chapter focusing on patient safety and another on an imaging modality not based on ionizing radiation – ultrasound. Finally, the last chapter of this book discusses future perspectives of the field of nuclear medicine.

This text will be an invaluable resource for libraries, institutions, and clinical and academic medical physicists searching for a complete account of what defines nuclear medicine.

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• The most comprehensive reference available providing a state-of-the-art overview of the field of nuclear medicine

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• Edited by a leader in the field, with contributions from a team of experienced medical physicists, chemists, engineers, scientists, and clinical medical personnel

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• Includes the latest practical research in the field, in addition to explaining fundamental theory and the field's history

1Principles behind Radiopharmacy

Thuy A. Tran and Erik Samén

DOI: 10.1201/9780429489501-1

Contents

1. 1.1History of Radiopharmacy
2. 1.2Basic Requirements for a Radiopharmacy
3. 1.3Workflow for Manufacturing of Radiopharmaceuticals
4. 1.4Methods for Synthesis of Radiopharmaceuticals
5. 1.4.1Kit-based synthesis
6. 1.4.2Automated synthesis
7. 1.4.2.1Cassette-based automated synthesis
8. 1.4.2.2Semi-automated synthesis with tubing systems
9. 1.4.3Manual synthesis
10. 1.5Some Trends and Developments in Radiopharmacy
11. 1.5.1Radiotheranostics concept
12. 1.5.2[¹⁸F]Aluminium fluoride radiolabelling of peptides
13. References

1.1 HISTORY OF RADIOPHARMACY

The first radiotherapeutics: The history of the existence of the radiopharmacy field originated mainly from the United States sometime in the late 1930s, when the first use of sodium iodide-131 was introduced by Hamilton and Soley [1]. In 1951 Sodium iodide-131 became the first radiopharmaceutical approved by the US Food and Drug Administration (FDA) for use in thyroid patients [2].

The first Single Photon Emission Computed Tomography (SPECT) radiopharmaceutical: One of the most important developments in radiopharmacy was in the early 1960s with the clinical introduction of ^99mTc generators for the preparation of radiopharmaceuticals by Powell Richards at Brookhaven National Laboratory [3]. Although more and more Positron Emission Tomography (PET) cameras are available, SPECT imaging using ^99mTc-labelled radiopharmaceuticals accounts for at least 80 per cent of all nuclear medicine investigations worldwide due to its low cost and availability.

The first PET radiopharmaceutical: Historically, ¹¹C is the first positron-emitting radionuclide was discovered in 1934 by Lauritsen and colleagues [4]. It proved to be very useful and was first studied in humans in 1945 by Tobias, who investigated the interactions of [¹¹C]carbon monoxide with red blood cells [5]. ¹¹C-labelled compounds are today frequently used, both in clinical routine and in PET research studies.

1.2 BASIC REQUIREMENTS FOR A RADIOPHARMACY

The procedures and requirements for operating a radiopharmacy are largely dependent on the nature of the radiopharmaceuticals that are to be produced and their intended use. As general principles, the following basics requirements apply:

• Good Manufacturing Practice (GMP): Radiopharmaceuticals are strictly regulated as they are both medicinal products and radioactive materials. A radiopharmaceutical must be produced in accordance with GMP. The applicable legislation and guidelines and how to implement them are well-reviewed by Lange and colleagues [6]. The GMP guidelines for medicinal products are well described in EudraLex Vol. 4 (EU GMP) [7], and in supplementary guidelines applied specifically for the manufacture of radiopharmaceuticals according to EU GMP Annex 3 [8]. More details on the GMP rules and recommendations are found in Chapter 8 in this volume, and further readings on the small-scale production of radiopharmaceuticals can be found in Gillings and colleagues [9].
• Design considerations of a radiopharmacy: One of the most important considerations, when constructing and designing a radiopharmacy, is to define early on the goals and scope of the radiopharmacy: What types of radiopharmaceuticals will it produce (manufacturing and/or compounding)? Will it be a centralized radiopharmacy, an industrial manufacturer and/or a PET centre? Will it produce established routine radiopharmaceuticals for nuclear medicine investigations, or will it also be a research centre? The radiopharmacy laboratories are then designed, constructed, and adapted to suit the purposes and operations to be carried out. These details are outlined in Chapters 5 and 7 in this volume. Useful reading on this topic can be found in Gillings and colleagues [9].
• Instrumentation and equipment needed: A large number of instruments and equipment are used in the production and quality control (QC) of radiopharmaceuticals. Essential equipment for the production of PET radiopharmaceuticals [such as Fludeoxyglucose F-18 (FDG)] includes cyclotrons (see further in Chapter 4 in Vol. I), hot cells, lead-shielded Laminar Air Flow (LAF) benches, synthesis modules, dose calibrators, and dispensers. A wide variety of equipment is also dedicated to the QC of radiopharmaceuticals before release for patient administration. These are, for example, high-performance liquid chromatography (HPLC) coupled with a radiation detector for analysing the radiochemical purity; a thin-layer chromatography (TLC) scanner for determining radiochemical impurities; gas chromatography (GC) for analysis of residual solvents such as ethanol, acetonitrile, or acetone; a pH-meter, equipment for checking endotoxin contents, bubble point tester for checking the filter integrity, and so forth. More about the methods and equipment for QC can be found in Chapter 6. Other critical instr...