chapter 1 What Is Nuclear Medicine?

a Fundamental Concepts

The science and clinical practice of nuclear medicine involve the administration of trace amounts of compounds labeled with radioactivity (radionuclides) that are used to provide diagnostic information in a wide range of disease states. Although radionuclides also have some therapeutic uses, with similar underlying physics principles, this book focuses on the diagnostic uses of radionuclides in modern medicine.

In its most basic form, a nuclear medicine study involves injecting a compound, which is labeled with a gamma-ray-emitting or positron-emitting radionuclide, into the body. The radiolabeled compound is called a radiopharmaceutical, or more commonly, a tracer or radiotracer. When the radionuclide decays, gamma rays or high-energy photons are emitted. The energy of these gamma rays or photons is such that a significant number can exit the body without being scattered or attenuated. An external, position-sensitive gamma-ray “camera” can detect the gamma rays or photons and form an image of the distribution of the radionuclide, and hence the compound (including radiolabeled products of reactions of that compound) to which it was attached.

There are two broad classes of nuclear medicine imaging: single photon imaging [which includes single photon emission computed tomography (SPECT)] and positron imaging [positron emission tomography (PET)]. Single photon imaging uses radionuclides that decay by gamma-ray emission. A planar image is obtained by taking a picture of the radionuclide distribution in the patient from one particular angle. This results in an image with little depth information, but which can still be diagnostically useful (e.g., in bone scans, where there is not much tracer uptake in the tissue lying above and below the bones). For the tomographic mode of single photon imaging (SPECT), data are collected from many angles around the patient. This allows cross-sectional images of the distribution of the radionuclide to be reconstructed, thus providing the depth information missing from planar imaging.

Positron imaging makes use of radionuclides that decay by positron emission. The emitted positron has a very short lifetime and, following annihilation with an electron, simultaneously produces two high-energy photons that subsequently are detected by an imaging camera. Once again, tomographic images are formed by collecting data from many angles around the patient, resulting in PET images.

b The Power of Nuclear Medicine

The power of nuclear medicine lies in its ability to provide exquisitely sensitive measures of a wide range of biologic processes in the body. Other medical imaging modalities such as magnetic resonance imaging (MRI), x-ray imaging, and x-ray computed tomography (CT) provide outstanding anatomic images but are limited in their ability to provide biologic information. For example, magnetic resonance methods generally have a lower limit of detection in the millimolar concentration range (≈ 6 × 10¹⁷ molecules per mL tissue), whereas nuclear medicine studies routinely detect radiolabeled substances in the nanomolar (≈ 6 × 10¹¹ molecules per mL tissue) or picomolar (≈ 6 × 10⁸ molecules per mL tissue) range. This sensitivity advantage, together with the ever-growing selection of radiolabeled compounds, allows nuclear medicine studies to be targeted to the very specific biologic processes underlying disease. Examples of the diverse biologic processes that can be measured by nuclear medicine techniques include tissue perfusion, glucose metabolism, the somatostatin receptor status of tumors, the density of dopamine receptors in the brain, and gene expression.

Because radiation detectors can easily detect very tiny amounts of radioactivity, and because radiochemists are able to label compounds with very high specific activity (a large fraction of the injected molecules are labeled with a radioactive atom), it is possible to form high-quality images even with nanomolar or picomolar concentrations of compounds. Thus trace amounts of a compound, typically many orders of magnitude below the millimolar to micromolar concentrations that generally are required for pharmacologic effects, can be injected and followed safely over time without perturbing the biologic system. Like CT, there is a small radiation dose associated with performing nuclear medicine studies, with specific doses to the different organs depending on the radionuclide, as well as the spatial and temporal distribution of the particular radiolabeled compound that is being studied. The safe dose for human studies is established through careful dosimetry for every new radiopharmaceutical that is approved for human use.

c Historical Overview

As with the development of any field of science or medicine, the history of nuclear medicine is a complex topic, involving contributions from a large number of scientists, engineers, and physicians. A complete overview is well beyond the scope of this book; however, a few highlights serve to place the development of nuclear medicine in its appropriate historical context.

The origins of nuclear medicine ¹ can be traced back to the last years of the 19th century and the discovery of radioactivity by Henri Becquerel (1896) and of radium by Marie Curie (1898). These developments came close on the heels of the discovery of x rays in 1895 by Wilhelm Roentgen. Both x rays and radium sources were quickly adopted for medical applications and were used to make shadow images in which the radiation was transmitted through the body and onto photographic plates. This allowed physicians to see “inside” the human body noninvasively for the first time and was particularly useful for the imaging of bone. X rays soon became the method of choice for producing “radiographs” because images could be obtained more quickly and with better contrast than those provided by radium or other naturally occurring radionuclides that were available at that time. Although the field of diagnostic x-ray imaging rapidly gained acceptance, nuclear medicine had to await further developments.

The biologic foundations for nuclear medicine were laid down between 1910 and 1945. In 1913, Georg de Hevesy developed the principles of the tracer approach ² and was the first to apply them to a biologic system in 1923, studying the absorption and translocation of radioactive lead nitrate in plants.³

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