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An overview of PET imaging in oncology


11 June, 2009  

PET imaging is used for staging, measuring the response to chemotherapy and/or radiotherapy, identifying prognosis and tumour recurrence, benign and malignant tumours, untreated malignant sites and residual disease

Rohit Tiwari, BSc MRes MBA, Lead Technologist
PET, CT and Nuclear Medicine, Department of Radiology
Cromwell Hospital, London, UK

Positron emission tomography (PET) is a non-invasive nuclear medicine-based imaging technique that uses high-energy positron-emitting radioactive isotopes as molecular probes. A positron is an anti-matter (antiparticle) electron – that is, it has the same mass as an electron but instead of a negative charge it possesses a positive charge. According to the principles of quantum physics, when matter interacts with anti-matter, annihilation takes place, resulting in the production of high-energy photons (or detectable gamma rays).

This process is employed in the medical applications of PET imaging. When a positronemitting radioisotope is injected into a patient, it travels a few millimetres in the body and
invariably interacts with an electron from the surrounding matter (eg, fat, tissues, water). This interaction results in emission of gamma photons, which are then detected by an array of opposing detectors in a PET scanner. This forms
the basis of PET imaging (Figure 1).

Just like CT imaging, PET is also a tomographic imaging technique. The collection of many annihilated events over a period of time provides enough data to produce several projections, resulting in a 2D image of the isotope distribution. Hence fast and reliable computer hardware is a key requirement of a PET system. Most vendors supply their own computer software programs for data image analysis and processing. All these computer packages have immense capability to capture, disseminate and process acquired data. The technical development of PET imaging as an in-vivo imaging technique has spanned several decades.

PET allows an accurate quantification of the distribution of radioactivity in the body and offers possibilities to study physiology, molecular biology, energy metabolism, drug–receptor or drug–enzyme interactions, and the fate of
radiotracers in living tissues.[1] Factors such as the biodistribution of the molecule of interest, its selectivity and its type of binding in the tissue are important considerations before selecting the tracer for PET imaging.[2]

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Currently used positron emitters
PET employs mainly short-lived positron-emitting radiopharmaceuticals. A crucial feature of these isotopes is that they are analogues of naturally occurring elements (apart from fluorine, which happens to be most widely used PET isotope). Table 1 lists some isotopes used.

For day-to-day clinical work, 18F labelled with fluoro-deoxyglucose (FDG) has become the nuclide of choice. It has a relatively “longer” half- life, which makes it easier to transport with a two-hour drive radius in a city. Since it is not possible for every medical centre to set up their own cyclotron, it is becoming increasingly commonplace that a cyclotron facility supplies 18F-FDG to PET centres in surrounding areas.

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PET in oncology
It was first observed in the 1930s that a malignant
transformation of cells is associated with an increased glycolytic rate. Accelerated glucose metabolism is present in a number of tumours. The most popular radiopharmaceutical of choice currently is 18F-FDG. FDG is a glucose analogue, which means that once it is injected it is transported to the cells which have an increased glucose demand and it is phosphorylated, but unlike the glucose molecule it remains trapped inside a cell long enough to allow optimum time for imaging. Since cancer cells have several times more glucose requirements than normal cells, they take up FDG in a higher concentration than the surrounding normal cells (Figure 2). This creates a differentiation in uptake and can be interpreted by a radiologist or nuclear medicine specialist.

On account of the similarity of the FDG molecule to a glucose molecule, it is possible to quantify the metabolic rate with various techniques. The most common quantification technique in clinical PET is SUV (standardised uptake value). SUVs are often used to differentiate malignant and benign tumours (a lower SUV value would indicate a benign aetiology). The indications for PET in oncology include:
 

  • Staging.
  • Treatment response to chemotherapy and/or radiotherapy.
  • Prognosis and tumour recurrence.
  • Distinguishing benign from malignant tumours.
  • Identifying untreated malignant sites.
  • Identifying residual disease.

One of the most important advantages of PET imaging is that it allows a whole-body scan in a single radioactive dose. This is of huge significance to reassure patients who are often anxious to find out whether the disease has spread elsewhere in the body. In the author’s experience it is not rare to find other cancer types or an unexpected site of the disease when it was not expected simply based on the patient’s medical history. FDG is not tumour-specific, but it will be taken up by any metabolically active cells (Figure 3).

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Various conditions can increase the metabolic activity of a cell, for example malignancy, inflammation and infection, so it is extremely important that a carefully designed clinical history is obtained before FDG injection. In the author’s institution, it is customary to obtain a clinical history that is relevant for the full optimisation of the FDG PET imaging. (The questionnaire is available from the author on request.)

Some of the most commonly used areas of cancer management where PET has proven to be a useful tool are listed in Table 2. The list is indicative only and includes some conditions very frequently referred for PET imaging in the author’s institution. As more data have become available, the importance of PET imaging has increased for diagnosis, staging and restaging for various cancer types. However, for certain cancer types such as lymphoma, PET imaging fares better than other techniques. In one study when PET was used to identify the presence or absence of disease in patients with Hodgkin’s lymphoma, both during the initial staging and during restaging, it was found to be 86% sensitive and 96% specific, compared with 81% sensitivity and 41% specificity for CT.3 A large body of literature demonstrates the use of PET in distinguishing benign from malignant cause for a pulmonary nodule.[4]

PET-CT imaging
The role of PET-CT imaging as a screening tool is not currently available due to legislative constraints. However, this may change when more data are available to develop understanding of risk to benefit of screening PET imaging, although currently requests for any PET-CT scan must be supported by a relevant clinical background.

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The newest development of PET scanners is a hybrid PET-CT scanner in which the same gantry unit houses both the PET scanner and the CT scanner. PET-CT is a unique diagnostic tool that combines the highly sensitive nature of isotope imaging with the high specificity of CT anatomical imaging, thus creating hybrid images, showing both physiological function and anatomical structures. These latest breeds of scanners have a much faster scanning time, and it is possible to reduce the administered FDG activity without compromising the image quality of a patient’s scan. Another major advantage of newer PET-CT units is that they allow a considerable reduction of scanning time. A conventional PET imaging session for a patient could last as long as 50–70 minutes. But with new scanner types this is usually reduced to 15–20 minutes, including the CT scanning time. Faster throughput means more patients can benefit from this technology and it is also cost-effective.

However, more research is needed to see whether a PET-CT scanner can actually replace a dedicated CT scanner in a hospital. It is the author’s opinion that such replacement would be extremely difficult as the operational logistics of PET and CT are different.

To fully optimise the capacity of PET-CT imaging, it is better to start thinking now along the lines of expanding the imaging portfolio in other directions too (eg, PET cardiology, treatment planning) as more applications of PET become clinically acceptable. However, shortlived tracers still pose a bottleneck in developing PET imaging.[5]

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Conclusion
PET imaging and PET-CT have now come of age, and they are regarded by several experts as the key part of a patient’s cancer management. Although the focus of this article has been solely on oncological applications of PET-CT, it must not be forgotten that PET-CT also has several applications in neurology and psychiatry, which are changing the way patients are managed within those specialties.

Future requirements of PET-CT will include radiologists trained in nuclear medicine imaging or vice versa, and nuclear medicine technologists with CT training. However, one can safely assume that PET-CT as an imaging tool is definitely heading for a brighter future

References
1. Comar D, editor. PET for drug development and evaluation,
development in nuclear medicine, Vol. 26. London: Kluwer Academic Publishers; 1995.
2. Lasne MC, Perrio C, Rouden J, et al. Chemistry of ß+-emitting compounds based on Fluorine-18. Topics in
Chemistry 2002;222:201-58.
3. Rodriguez M, Rehr S, Ahlstrom H, Sunsstrom C, Glimelius B. Predicting malignancy grade with PET in non-Hodgkin’s lymphoma. J Nucl Med 1995;36:1790-6.
4. Rohren EM, Turkington T, Coleman R. Clinical applications of PET in oncology. Radiology 2004;231:305-32.
5. Knutti J. Should we use more PET-CT in clinical cardiology? Eur J Nucl Med Mol Imaging 2008;35:887-8.