1
Positron Emission Tomography

Juan José Vaquero1 and Stephen L. Bacharach2

1 Universidad Carlos III de Madrid and Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

2 University of California at San Francisco, San Francisco, CA, USA

Introduction

The goal of all cardiac nuclear imaging is to trace the fate of radioactively labeled biochemical compounds (tracers) within the body, usually in the myocardium or blood pool. One usually either makes a static image of the distribution of the radiotracer (e.g., technetium‐99m (99mTc) sestamibi (methoxyisobutylisonitrile or MIBI) or thalium‐201 (201Tl)) or follows the uptake and clearance of the tracer with time. In the former case, static imaging is all that is required, while in the latter a series of images, acquired dynamically over time, is necessary. Positron emission tomography (PET) has these same goals. Although PET works in a manner very similar to conventional tomographic nuclear imaging techniques (e.g., single photon emission computed tomography or SPECT), there are some very significant differences. It is these differences that make PET of great potential value in nuclear cardiology, and it is these differences we will emphasize in this chapter.

Positron Decay

PET tracers, as their name implies, decay by emission of a positron. Except for their opposite charge, positrons are nearly identical to ordinary negatively charged electrons (which in fact are often called “negatrons”). They have the same mass and behave similarly when passing through the body. Positrons, however, are the “antimatter” of electrons. When a positron and an electron are in close proximity for more than the briefest interval, both will disappear (an event called “annihilation”), and their masses will be converted into energy in the form of two gamma rays traveling in almost exactly opposite directions. The energy of each photon is 0.511 MeV (precisely the equivalent energy corresponding to the mass of the electron or positron). These photons are sometimes called “annihilation” photons. The two photons travel in nearly exactly opposite directions in order to conserve momentum. The entire process is illustrated in Figure 1.1. In this figure it is assumed that a positron emitter (in this case carbon‐11 (11C)) is part of a tracer somewhere in the body (e.g., the myocardium). When the positron is emitted from the nucleus it is traveling at very high speed, nearly the speed of light. It moves through the tissue just as an electron would, bouncing off many of the atoms and losing energy as it does so. The final distance between the original atom and the annihilation point is called the “positron range.” Eventually (typically within a millimeter or so, depending on the radionuclide) it slows down enough to spend a significant time near an electron. As soon as this happens the two annihilate and the two gamma rays (each with 0.511 MeV) are emitted, as shown in Figure 1.1, each going in nearly the exact opposite direction. Although in the figure the annihilation photons are shown traveling in exactly opposite directions, occasionally photons are emitted a few tenths of a degree more or less than 180° apart.

Figure 1.1 A positron is shown being emitted from the nucleus of 11C. It is assumed that the 11C atom is located in tissue. The positron is initially emitted at a speed which is a significant fraction of the speed of light. As it passes through the tissue, it gradually slows down, as it bounces off the atoms in the tissue. Eventually it slows down sufficiently so that it spends significant time near an atomic electron—its antimatter equivalent. When this happens the electron and the positron both annihilate—their mass being converted to energy in the form of two 511‐keV photons traveling in opposite directions, as shown.

PET scanners detect pairs of gamma rays resulting from annihilation. By determining where these two gamma rays (and all other pairs of gamma rays) originated, the PET scanner can produce an image showing the location in the body where the positrons were annihilated. However, if the positron has traveled far from its parent atom, the image will be inaccurate since the locus of the annihilating positron will not correspond to the locus of the radioactive atom. For this reason the initial speed (i.e., energy) of an emitted positron will affect the capacity of the PET scanner to accurately define the position of radioactive atoms within the body (e.g. the myocardium). This in turn affects the ultimate spatial resolution of the images that can be obtained with a PET scanner.

There are many radioisotopes that emit positrons, and so would be suitable for use with a PET scanner. Several of the most important ones are listed in Table 1.1, along with their half‐lives and some characteristics of the positron that is emitted [1]. One of the reasons why PET has played such an important role in basic research is that several of the radioisotopes that are positron emitters (carbon, nitrogen, and oxygen) are the basic building blocks of all physiologically important biochemical compounds. This has permitted researchers to label amino acids, glucose, and a host of other biochemical compounds. Unlike the case with 99mTc and other heavy metals used in SPECT imaging, the labeling of PET tracers can often be done without making any alterations to the biochemical structure of the compound of interest. That is, a nonradioactive 12C atom can be replaced with a 11C atom, so that the resultant radiolabeled biochemical compound behaves just like the unlabeled one. The difficulty with 11C, nitrogen‐13 (13N) and oxygen‐15 (15O) is that their half‐lives are very short. This means they must be produced locally with an on‐site cyclotron. It also means that the chemist in charge of labeling the biochemical compound of interest has very little time to do so. For these reasons (and others discussed later in this chapter), the two most clinically important positron‐emitting isotopes for cardiology are the last two on the list, rubidium‐82 (82Rb) and fluorine‐18 (18F).

Table 1.1 Positron energies and ranges (in tissue).

*82Rb emits two different positrons. Eighty‐three percent of the time it emits a 3.35‐MeV maximum energy positron and 12% of the time a 2.57‐MeV positron.

18F has a 2‐hour half‐life. This is long enough to allow production at a site up to an hour or two away. The recent dramatic increase in the use of fluorodeoxyglucose (18FDG) for tumor imaging has resulted in a large number of such commercial production sites, and one can easily arrange for daily delivery of unit doses. 18FDG has proven very valuable in assessing myocardial viability [2]. Its use for this purpose, in the past, was limited to large research institutions because of the lack of availability of 18FDG and a PET scanner. As mentioned, 18FDG is now widely available commercially, and there are a huge number of new PET scanners installed, the majority in nonresearch hospitals. Although most of these scanners were installed for oncology imaging, the machines are suitable for cardiac imaging as well.

The other clinically important radiopharmaceutical in Table 1.1 is 82Rb. This is a potassium analog and can be used to measure myocardial perfusion [3]. No labeling is required. Although it has a very short half‐life (76 seconds), it can be produced from a longer lived rubidium‐82 (82Sr) generator, with a half‐life of 25 days. At the moment such generators are expensive, but their cost is dropping as demand increases.

Aside from half‐life, two other factors must be considered when determining the utility of a positron‐emitting isotope. First, it is important that nearly all the decays are by positron emission, rather than by other forms of decay whose emissions cannot be imaged with a PET scanner. 11C, 13N, 15O, and 18F all decay nearly 100% of the time by positron emission, and 82Rb decays about 95% of time by positron emission [4]. The remaining fraction of the decays is by electron capture, a process that produces radiation that cannot be imaged with a PET scanner. In addition, for 82Rb, a small fraction (~12%) of the positrons are accompanied by an additional high‐energy gamma ray (0.778 MeV) which can...