The contribution of medical physics to nuclear medicine: a physician's perspective

This paper is the second in a series of invited perspectives by four pioneers of nuclear medicine imaging and physics. A medical physicist and a nuclear medicine clinical specialist each take a backward look and a forward look at the contributions of physics to nuclear medicine. Here is a backward look from a nuclear medicine physician's perspective.

speciality. It also represents the ideal setup, where an identified problem, namely, the investigation of thyroid physiopathology, led to the development of a new investigative tool (the radionuclide). It would take many years indeed before another 'magic bullet' was to be identified and widely applied. If specificity is intended by such a magic bullet, receptor ligands such as those targeting the dopamine and somatostatin receptors and most recently those ligands targeting the misfolded amyloid protein, are good examples of the progress achieved.
Whilst on the topic of interdisciplinarity, it is opportune to underline that not only physicists greatly contributed to the development of Nuclear Medicine. This equally applied inter alia to engineers, chemists and radiopharmacists. Gopal Subramanian with a degree in chemical engineering introduced 99m Tc labelled phosphonates for bone scanning; Hal Anger as an electrical engineer and biophysicist developed the Anger gamma camera; Roger Ekins, also a biophysicist, developed the saturation analysis/ radioimmunoassay methodology (Table 3). Physicists turned physiologist developed and emphasised the need for elegance and simplicity in quantitative measurements.
From the preceding paragraph, it is clear that fundamental discoveries spanned a period of a century. In the space available for this short piece, it is simply not possible to give due consideration to all those many eminent scientists who developed the field. So I shall focus on the three seminal physics developments which fundamentally changed the practice and future of Nuclear Medicine: the introduction of the rectilinear scanner, the development of the gamma camera and, finally, the design of the first single-photon emission computed tomography (SPET), positron emission photography (PET) and PET/computed tomography (CT) instruments.  Surface counting had been an important milestone in the clinical development of the radioactive tracer method. It was used early on by Norman Veal and others in mapping the placenta, the thyroid and the pericardium. This was laborious, a manual-driven process and rather time-consuming. It was difficult to perceive much more than the simplest outlines of organs, and yet, quantitative measurements were already taking place.
The relationship between physicists and physicians has always been most interesting. A healthy diffidence between both experts was often present and wonderfully illustrated from the following extract, taken from the outstanding chronology authored by Marshall Brucer, the first President of the Society of Nuclear Medicine (USA) and Chairman of the medical division of Oakridge Institute of Nuclear Studies from 1948 to 1962. And one can read in page 291: '…three months after the London meeting (the first meeting at University College London, on 29th July 1950, where data from 131 I  therapy was discussed)' , Sam Seidling asked: 'If a metastasis has high uptake, we can destroy it. Now, for God's sake, when will physicists learn to measure 131 I uptake?'. Leo Marinelli murmured: ' As soon as physicians decide how much uptake is high'. Benedict Cassen changed all this with his discovery of the rectilinear scanner in 1950. Born in New York in 1902, he graduated in physics and mathematics from the Royal College of Science in London in 1927. He moved to the California institute of Technology in 1930. Imaging the thyroid, he reported first results in 1950. The radioactive tracer method would forever be linked to imaging, for better or for worse. Single-head, dual-head, 3-inch or 5-inch rectilinear scanners and whole-body scanners became routine imaging instruments for 2D organ imaging and counting, dominating for some 30 years Nuclear Medicine applications well into the late 80s, as new tracers became available.
Whilst brilliant individual scientists made major contributions to medicine, institutions and or societies have a habit of getting it wrong. In the late 40 s, much debate and thought went into what role a medical physics department should have in a hospital. To quote an example: '…Any one radio-element investigation may be too short lived to justify the provision by the department concerned of the best apparatus for the job'. [4]. Whilst Cassen had already proven that this viewpoint was completely wrong, how would Hal Anger comment on the on the previously mentioned discussion?

US patent 3,011,057 in 1961
Nuclear Medicine was to change forever with the mentioned patent, defining the Anger gamma camera. It is truly astonishing that this technology, still in worldwide use today, has outlived over half a century of technological breakthroughs and progress! In modern times, there is probably no other example of such a long lasting instrumentation breakthrough.
Hal Oscar Anger (Figure 2) was born on the 20th of May 1920, in Denver, USA. He graduated as an electrical engineer. His innovative career spanned from radar jamming equipment to radiation detector devices, culminating with his seminal invention of the It would take some 30 years before 3D Imaging became an integral part of the development of Nuclear Medicine. And one has to give proper due to a medical scientist, David Kuhl (Figure 3) Single-slice SPET imaging was subsequently superseded by whole-volume SPET imaging, with the introduction of the rotating gamma camera (Anger's device, shaping de novo the clinical applications of the radioactive tracer method). Without SPET, nuclear cardiology, and less so, neurotransmission imaging would have not risen to the clinical pre-eminence these modalities reached in the last 15 years. SPET became a truly worldwide available technology, supported by a range of useful radiopharmaceuticals.

Modern technologies (SPET, SPET/CT, PET, PET/CT and PET/MR)
The beginnings and development trends of positron emission tomography are outlined in Table 4. Again, constraints on space prevent a detailed analysis. Suffice to say that for a physician, interested in patient care and management, it took a rather long time before clinical useful applications began to emerge [5][6][7]. It would take the development and final availability of 18 F labelled glucose, which made positron emission tomography a clinically useful tool. Between the development of the first PET system in 1973 by Michael Phelps and the approval by the FDA of 18 F labelled glucose, 24 years would have elapsed (Table 4).
To complete this brief review, we end with David Townsend, Ph.D., who gave us the most significant development in medical imaging in the last 10 to 15 years. The PET/ CT prototype, attributed to Townsend and Nutt (Figure 4), then President of CPS Innovations, was named by TIME Magazine as the medical invention of the year 2000. A hugely impressive development, bringing human anatomy and biochemistry onto a combined 3D map, this technology was instantly adopted by the medical community as  an essential tool for early staging and monitoring of human disease. No hospital facility today can bypass the availability of a PET/CT system for appropriate patient management. What about PET/MR? Time will tell; its adoption by the medical community will take much longer. But the input of physics computing and engineering will remain vital for the future development of this innovative speciality. This will be ever more relevant as the demands posed by multimodality imaging technologies and the need for true quantitative and reproducible measurements are widely felt. This is especially relevant in the increasing need for the monitoring of interventions, being medical, surgical or pharmacological, applied to an individual patient. Whilst the overtly simplistic aims of personalised medicine are being reassessed, patient specific interventions will grow, and with it, the growth of physics in the field is assured.