Positron emission tomography (PET) represents the most advanced scintigraphic imaging technology. It can be employed for cardiovascular research as well as for clinical applications in patients with various cardiovascular diseases. PET allows non-invasive functional assessment of myocardial perfusion, substrate metabolism and cardiac innervation and receptors as well as gene expression in vivo. PET is regarded as the gold standard for the detection of myocardial viability, and it is the only method available for the quantitative assessment of myocardial blood flow.

Despite these facts, PET has been applied to only a modest extent in routine clinical cardiology. The current striking increase in clinical PET in oncology will resolve the most important limitation of PET—the availability of the technique. Thus, one might assume that clinical cardiac PET will undergo significant growth in the near future. However, there are many other excellent techniques for cardiac imaging. What might be the future role of PET in cardiology?

In studies of myocardial perfusion, the advantages of PET are measurement in absolute terms, attenuation correction and, due to the short half-lives of the tracers, the brevity of the procedure. Among the non-invasive methods, PET has been shown to achieve the highest diagnostic accuracy in the detection of coronary artery disease [1]. In addition, the sensitivity of PET for the detection of regional abnormalities has been found to be very good. An important limitation, however, is the continuing lack of large clinical studies providing information on the prognostic value of absolute perfusion data. One may also argue that the achieved improvement in accuracy as compared with single-photon emission tomography (SPET) is insufficiently significant to justify the use of a more demanding and expensive technique, especially when gated SPET with attenuation correction becomes routine. The unique feature of quantitative flow measurement is that it allows evaluation of very early changes in coronary vasoreactivity and the progression or regression of CAD at an early stage. When we learn more about the clinical and prognostic significance of these early abnormalities, the use of PET as a routine clinical tool may be justified.

Evaluation of myocardial glucose utilisation with fluorine-18 fluorodeoxyglucose ([18F]FDG) and PET is currently considered the most reliable tool for the identification of myocardial viability. The main value of non-invasive assessment of viability and hibernation is in the more severely and chronically disabled patient, in whom the outcome without intervention is poor but the risk of revascularisation is high. Viability is associated with a favourable long-term prognosis when patients are revascularised but with an unfavourable prognosis when patients are treated medically. However, large prospective randomised trials investigating the clinical and prognostic value of viability-guided treatment have not yet been published, and this represents a major limitation. Despite the recognised value of [18F]FDG PET in predicting improvement of left ventricle function after revascularisation, surprisingly wide ranges have been reported for sensitivity (71%–100%) and, in particular, for specificity (33%–91%) [2]. The variable results are probably related to differences not only in study populations but also in imaging protocols. Thus, optimisation and standardisation of [18F]FDG imaging protocols in a clinically challenging group of patients seem critical for the future.

In addition to [18F]FDG, there are many other metabolic tracers which have clinical potential, especially the fluorine-18 labelled tracers such as 18F-labelled 6-thia-hepta-decanoic acid ([18F]FTHA) [3, 4]. However, the real value of these tracers is unknown since larger clinical trials are unavailable. One potential tracer for clinical use is carbon-11 acetate, which allows robust non-invasive measurement of myocardial oxygen consumption in both the left and the right ventricle [5, 6]. This provides a means of estimating the oxygen cost of contractility, the efficiency of myocardial forward work, which is a parameter that seems to have clinical potential. These methods need to undergo further clinical studies before becoming part of the management approach in patients with heart disease.

A unique feature of PET is its value in the study of cardiac neurotransmission and receptors at the molecular level. The autonomic nervous system plays an important role in the regulation of cardiac function, and the regional distribution of cardiac nerve terminals can be visualised using scintigraphic techniques. A number of labelled analogues of norepinephrine have been investigated but the most commonly used PET tracer is [11C]hydroxyephedrine. In patients with heart failure secondary to either ischaemic heart disease or cardiomyopathy, reduced myocardial retention of the tracer is an adverse prognostic sign, presumably indicating advanced disease with denervation. Treatment with beta-blockade leads to parallel improvements in tracer uptake and symptoms, and similar observations have been made after cardiac transplantation. Further clinical studies are required before the clinical value of these observations is known. Although [11C]hydroxyephedrine is considered a more specific tracer than iodine-123 metaiodobenzylguanidine ([123I]MIBG), there is considerable less evidence supporting its clinical use. In addition, the short half-life of 11C limits its wider clinical use, and the 18F-labelled tracers such as [18F]fluoronorepinephrine may have greater clinical potential. Tools to investigate beta-receptors, alpha-1 receptors, adenosine receptors and muscarinic receptors have also been developed for PET, but the clinical data are still very limited. Myocardial beta-adrenoceptors were found to be downregulated after myocardial infarction and the receptor density was able to predict left ventricular volumes at 6 months [7].

The new imaging targets may become more important when new therapies are developed. The imaging of vulnerable arteriosclerotic plaque [8] and gene transfer imaging techniques [9] have great clinical potential. It is to be noted that many of these new targets require better resolution and sensitivity, giving PET a clear advantage over SPET.

Novel applications also depend on improved instrumentation. The development of hybrid PET-CT scanners and especially the recent multislice CT/PET systems may fundamentally change the field of cardiac imaging. These systems potentially allow comprehensive imaging of cardiac function with anatomical co-registration, e.g. coronary anatomy and quantitative perfusion can be studied in a single session of less than 1 h. In addition, it is important to note that for the imaging of many new targets, such as plaque or gene expression, fusion imaging may be a prerequisite for accurate interpretation.

It seems likely that there will be a future trend towards personalised medicine. This means that the demanding and expensive therapies of the future will need to be targeted to carefully selected subpopulations. Imaging techniques, and especially molecular imaging, could play a pivotal role in this process [10]. PET provides a unique and powerful method to bridge the gap between molecular biology, pathophysiology and targeted therapy.