Introductory Chapter: Dosimetry in Radiopharmacy

1. Introduction

Nuclear medicine and radiopharmacy are based on the scientific ideas and discoveries of the beginning of the last century and are decisively shaped by their respective discoverers. Among them are H. Becquerel, M. Curie & P. Curie (Nobel Prize 1903 “discovery of spontaneous radioactivity” and “researches on radiation phenomena…”), I. Curie & F. Joliot (Nobel Prize 1935 “synthesis of new radioactive elements”), G. de Hevesy (Nobel Prize 1943 “for the use of isotopes as tracers in the study of chemical processes”), O. Hahn, F. Strassmann, L. Meitner & O. R. Frisch (Nobel Prize 1944 only to O. Hahn “Discovery of the fission of heavy nuclei”), R. S. Yalow & S. A. Berson (Nobel Prize 1977 only to R. S. Yalow “Development of radioimmunoassays of peptide hormones”) or Saul Hertz and Arthur Roberts [1, 2].

Based on their fundamental discoveries, the two closely intertwined disciplines developed further and established their place in the clinical routine. Today, radiopharmaceuticals are indispensable to clinical diagnosis and therapy for various diseases [1].

Growing experience in radiochemistry and its fusion with organic chemistry further facilitated the application of radionuclides and radiolabeled compounds in medicine. All this was accompanied by continuous technical development, driven by the natural sciences and industry, which provided the appropriate equipment and invaluable contributions from other disciplines such as mathematics, physics, and biology. In every respect, radiopharmacy or radiopharmaceutical chemistry is an excellent example of the interdisciplinary nature of modern science and technology.

Unnoticed by the general public, technetium-99 m, a radioisotope of a biologically irrelevant element, is used in millions of diagnostic procedures yearly. Various tracers are radiolabeled to cover a wide range of diagnostic applications. In addition, an ¹⁸F-radiolabeled derivative of the most abundant monosaccharide, glucose, plays an essential role in quantifying glucose metabolism, which can indicate severe disease, although the derivative does not exist naturally.

The spectrum of available radiopharmaceuticals ranges from non-specific perfusion tracers to highly selective, targeted tracers suitable for various applications (both diagnostic and therapeutic). Some of these radiopharmaceuticals have been used in routine clinical use for decades. These include iodine- and technetium-labeled compounds. Highly specific, targeted tracers have become increasingly important over the past decade. Despite their relatively short history of routine use, their impact on nuclear medicine has been profound. This is particularly evident in the ever-increasing number of approved radiopharmaceuticals and clinical trials. Radiopharmacy and nuclear medicine are new growth markets [3]. Today, the influence of radiopharmaceutical chemistry extends far beyond supplying radiopharmaceuticals to nuclear medicine centers. It also plays a crucial role in industrial drug development and fundamental biochemical and medical research.

The development of radiopharmaceuticals is a complex, interdisciplinary process that depends on many factors. It begins with the selection of a suitable radionuclide. Its physical properties must match the type of application. For radiolabeling, its chemical properties must match those of the selected precursor. The radionuclide and the precursor must be available in the highest quality and quantity. During the reaction, the precursor must not be degraded or destroyed by the reaction conditions or the radiation to achieve acceptable (activity) yields. Pharmaceutical standards must be consistently maintained. In addition, the radioactive decay and half-life of the radionuclide determine every step of the process, from the start of radionuclide production to its final use in the patient. Transport, storage, and patient management are more complex and susceptible to disruption than traditional non-radioactive drugs. Nonetheless, nuclear medicine is an integral part of precision medicine, with an ever-increasing demand for radiopharmaceuticals in patient care.

The development, preclinical, and clinical evaluation of new radiopharmaceuticals involves the identification and targeted use of novel molecular targets for effective and efficient imaging and therapy. This includes binding modeling, biodistribution, pharmacokinetics, process optimization, (further) development of suitable manufacturing and quality control methods, and dosimetry studies. All this ultimately leads to an optimized, automated synthesis of pharmaceutical-grade radiopharmaceuticals.

Radiotherapy and radiopharmaceuticals aim to increase the life expectancy of cancer patients; however, this increase is accompanied by the risk of subsequent radiation-induced secondary cancers, which poses a significant challenge. To prevent a reduction in life expectancy, dosimetry is essential at various points in radiopharmaceutical therapy, from pre-treatment planning through the absorbed dose to the target organ or tumor to the total body dose.

Dosimetry studies in radiotherapy aim to calculate the dose absorbed by normal tissues and tumors and anticipate radiation’s biological effects. Absorbed dose calculations take into account (patient-dependent) anatomy, radiopharmaceutical biodistribution, and (patient-independent) radionuclide properties [4]. Therefore, the role of medical physicists is to ensure the safety of patients undergoing radiotherapy by ensuring that the radiotherapy equipment is correctly calibrated and delivers accurate radiation.

Radiotherapy dosimetry methodologies must take into account the types of radionuclides, i.e., low (beta particles and photons) and high (alpha particles) linear energy transfer emitters, for effective treatment planning [5]. In conclusion, improvements in dosimetry studies will help develop new advances in radiotherapy for improved efficacy, leading to fewer complications.