90 years after the discovery of the positron – positron emission tomography has become a unique diagnostic and theranostic tool

No one would probably have foreseen the role that a tiny elementary particle would play decades later in the world of nuclear medicine imaging. In fact, it was 90 years ago that Carl David Anderson accidentally discovered the positron in 1932 during experiments to detect cosmic rays and provided the correct interpretation. This was indeed a sensational discovery, for only four years earlier Paul A. M. Dirac had presented his relativistic wave equation for fermions, which not only explained the spin-1/2 nature of the electron, but also predicted the existence of the electron's antiparticle. The fact that antimatter should exist was at that time an almost unbelievable hypothesis and a claim shaking all foundations of established physics. No wonder that the experimental physicists rushed to the proof of this antiparticle – the antielectron.

Carl David Anderson was born in New York City (USA) in 1905. He studied physics and engineering at the California Institute of Technology (Caltech), graduated with a bachelor’s degree in 1927, and finished his PhD in 1930 under the supervision of Robert A. Millikan. Afterwards he had the opportunity to continue working with Millikan as a research fellow to study cosmic rays [1].

To analyse cosmic rays, Anderson used a vertical cloud chamber, also known as Wilson chamber, with a strong water-cooled electromagnet with a magnetic field of 15,000 Gauss (1.5 Tesla) [2]. For the experiments, he transported it to the summit of Pikes Peak (4300 m) in the Rocky Mountains near Colorado Springs, USA. To distinguish whether a particle was moving upwards or downwards, he added a 6 mm thin lead plate into the chamber. After passing this plate, the radius of the particle’s track curvature is smaller, and thus the direction can be determined [2], [3]. While he analysed the photographed tracks produced by cosmic rays in the Wilson chamber on August 2, 1932, he realised, that some tracks (15 out of 13,000) could not have been produced by electrons but by particles with a positive charge, as their curvature was opposite to that of an electron [2], [4].

Due to the similar radius, it could not be a proton, but it had to be a particle with a mass in the same order of magnitude as the electron [4], [5]. He called these particles positrons. One of the first photographs of a positron track through a 6 mm lead plate taken by Anderson in 1932 is shown on the title page of this issue. Anderson was awarded the Nobel Prize for his discovery of the positron in 1936, which he shared with Victor Hess.

Patrick Blackett and Giuseppe Occhialini worked on the same topic at the Cavendish Laboratory in Cambridge, UK. However, Anderson was faster with his accidental discovery, but Blackett and Occhialini succeeded in confirming Anderson’s discovery in 1933 [6]. It was also Blackett and Occhialini who developed, based on Dirac’s theory, the concept of pair production by high-energy nuclear collisions and the reverse process – the annihilation – in which an electron and a positron collide to produce two photons [7]. Each of these photons have an energy of 511 keV and move in opposite directions.

From these basic scientific findings, it took nearly two decades before the first positron-emitting radionuclides could be used for localising brain tumours in the early 1950s [8], [9], [10]. For example, in 1953, Brownell and Sweet described in detail the use of the coincidence detection to localize brain tumours using copper 64 (⁶⁴Cu) and arsenic 75 (⁷⁵Ar) [10], [11], [12]. In fact, ⁶⁴Cu-labelled ligands are still in use today. For example, Bailey et al. [13] describe one of the most recent theranostic applications of this positron emitting radionuclide.

The introduction of emission and transmission tomography by David E. Kuhl and Roy Q. Edwards in 1968 [14] and the development of transverse axial tomography for radiography by Godfrey Hounsfield [15] led to the development of the first “positron emission tomography” (PET) scanner using filtered back projection by Michel Ter-Pogossian, Michael E. Phelps, and Edward J. Hoffman in 1975 [11], [16], [17]. The development of ¹⁸F labelled 2-fluorodeoxy-D-glucose (¹⁸F-FDG) in 1978 by Ido et al. [18] laid the foundation for functional imaging in oncology and is therefore the reason for the success of PET imaging today [19].

Since then, continuous advances in the technical and material components of positron emission tomography have led to highly sensitive spatial detection of annihilation photons. Combined with sophisticated image reconstruction techniques and the rapidly growing development of new radiopharmaceuticals, this has led to vastly improved patient diagnostics available today. Today's positron emission tomography would not have been possible without the discovery of the positron and the physical properties of positron annihilation 90 years ago. In today's medicine, PET has thus become a unique diagnostic and theranostic tool for quantitative imaging of physiological and pathological metabolic processes.

The articles in this special issue focus mainly on PET and provide an overview and insights into some of the recent developments in nuclear medicine imaging and therapy.