The picture of PET scanning

CRC for Biomedical Imaging Development (CRCBID) explains why PET scanning sets the standard of care in the modern healthcare sector.

What is PET?

Positron Emission Tomography (PET) scanning is a unique functional diagnostic imaging tool that sets the standard of care in the modern healthcare sector. PET can be used to image and measure the human body’s biochemical and physiological function. The information gained from a PET scan is invaluable because functional changes caused by disease are frequently detectable before any structural abnormalities become evident. It is mainly used to determine the presence and severity of cancers and in clinical practice it is central to characterising, staging and follow-up for patients with a wide variety of malignancies. Studies demonstrate that PET offers significant advantages over other forms of imaging such as CT or MRI scans to diagnose and manage disease. In fact, PET images are now generally combined with Computed Tomography (CT) systems that offer an image of the structure (anatomy) of the body by using X-rays. PET/CT scanners produce a fused image of the distribution of tracers in the body, superimposed on an anatomical map.

How does PET work?

PET is an example of nuclear medicine, which means it depends on the use of radioactive isotopes made in cyclotrons or nuclear reactors. A radioactive isotope is a chemical element with an unstable nucleus that, over time, decays into more stable isotopes, emitting subatomic particles in the process. When a radioactive atom such as fluorine-18 or carbon-11 decays, a proton in the atom’s nucleus turns into a neutron and emits a positron. The positron is a subatomic particle, identical to the electron except that it has the opposite electrical charge. When the positron collides with an electron in another atom, both particles are annihilated; that is, they are turned into energy, which radiates away as highly energetic gamma rays.

A PET machine can detect the gamma rays and calculate the location of the positron before it was annihilated with an accuracy of several millimetres. Medicine can exploit this phenomenon by using radioactive tracers (or radiotracers for short). The radiotracer is injected into a patient’s blood and concentrates in certain cells, for example, cancer cells that are said to ‘take up’ more of the tracer. A widely-used radiotracer is fluorodeoxyglucose (FDG), a molecule similar to glucose, and hence it is used to trace cells that consume large amounts of glucose, such as those that have become cancerous. The FDG molecule contains a radioactive fluorine atom that decays (usually within several hours) and subsequently emits a pair of positrons that are detected by the PET scanner.

Combining the results of millions of these detections, it is possible to build a detailed, three-dimensional map or image of the tissue or organ where the tracer has become concentrated in the body. The technique of combining all the detection data into a map or image is known as tomography. The high-resolution PET images are a powerful tool for doctors to diagnose disease early and aid their decisions about how best to treat the disease. It is often the best way to clearly identify the location and extent of an abnormality such as a tumour, and especially to assess response to treatment and to detect relapse.

PET can also reveal abnormalities in the body’s functions over a period of time, which makes it possible to investigate disorders such as epilepsy and heart disease. Clinicians also use an imaging tool known as single photon emission computed tomography, or SPECT for short. SPECT is a similar technique to PET but generally it is considered to be less powerful than PET. SPECT scanners usually use radiotracers with longer half lives than those used with PET (e.g. technetium-99m) and can therefore investigate longer-lasting functions in the body than those typically examined with a PET scanner.

What’s available today?

The indications for which PET/CT is funded in Australia are more limited than in some other developed countries. Medicare rebates are available for a variety of clinical conditions including:

• Solitary pulmonary nodule


• Metastatic/malignant melanoma


• Non-small cell lung cancer


• Colorectal carcinoma


• Ovarian carcinoma


• Uterine cervix


• Head and neck carcinoma


• Lymphoma


• Glioma


• Sarcoma


• Squamous cell carcinoma with cervical node involvement


• Oesophageal cancer


• Refractory epilepsy (non-oncologic)

The Australian community has never been as well informed about its treatment options than today. Online information sources and the sharing of experiences mean that patients and their families come to consultations having done research about what might be possible for their treatment. In addition, there are more technological choices and tools available to physicians to gain information about their patients’ conditions. PET/CT is one of those options. In the future, it will be possible to choose the most appropriate technology platform, then choose the right radiopharmaceutical tracer to target and identify a disease state. Both of these tools will then be used to develop a personalised therapy plan for each patient’s specific condition and treatment.

New research

Researchers and participant organisations from the Cooperative Research Centre for Biomedical Imaging Development Ltd (CRCBID) are leading the push to develop targeted tracers that can provide more options for personalised healthcare. These novel radiotracers have resulted from CRCBID’s research program, which is focussed on assisting clinicians to improve patient management.

Melanoma

Melanoma is a deadly form of skin cancer; its incidence is rising faster than any other cancer world wide, with about 160,000 new cases diagnosed each year. If not removed in its early primary stages the cancer is very difficult to cure. A tracer known as MEL050 has been developed by CRCBID researchers from initial work undertaken at the Australian Nuclear Science and Technology Organisation (ANSTO) in Sydney. MEL50 binds to melanin which is contained in melanoma cells. Their identification using MEL050 would be potentially very useful for clinical management of melanoma, a niche area of oncology. A phase 0/1 clinical trial was successfully completed late in 2011 at the Peter MacCallum Cancer Centre in Melbourne, using MEL050 made by Cyclotek (Aust) Pty Ltd. The trial aimed to prove the tracer’s safety in humans.

Solid tumours in the body

Fluoro propyl methionine (FPM) is a new amino acid tracer which is designed for use with a wide range of tumour types. After considerable pre clinical research, a phase 0/1 clinical trial is being conducted at Peter MacCallum Cancer Centre. This trial is also designed to prove safety of the tracer’s dosage in humans, and follows a first time in human (FTIH) review of the tracer’s manufacturing process at Peter MacCallum Cancer Centre (see image 2).

Brain tumour

A novel radiopharmaceutical tracer developed from an amino acid may provide better detection of brain tumours than FDG. A pilot study conducted by CRCBID researchers at Royal Melbourne Hospital investigated the diagnostic value of using FET (fluoro ethyl tyrosine) in conjunction with PET, rather than FDG with PET, to diagnose brain tumours.

The study results showed the excellent sensitivity of FET in comparison to FDG, when assessing a brain tumour, and especially in low-grade gliomas. Clinical studies continue to test the efficacy of substituting FET for FDG in diagnosing and managing brain tumours.

In January 2011, a PET scan using FET produced by Cyclotek was conducted at Wellington Hospital in New Zealand. The assessment showed that the FET PET scans provided better information, which improved the planning of surgery, and resulted in a less invasive procedure to remove the brain tumour.

The changing health landscape

Healthcare today allows medical professionals to offer more individualised treatment for their patients, targeting specific needs and particular conditions. This healthcare paradigm shift is being driven by a combination of factors, including:

• Advances in technologies;


• A greater understanding of genetics; and,


• Improved knowledge about the physiological basics of disease.

Advances in biomedical imaging allow increasingly precise and accurate diagnostic information to be gathered, leading to improvements in treatment of conditions such as cancer, and neurological disorders such as epilepsy and stroke. In cancers, for example, many tumours originating in a particular organ (i.e. the bowel) have the same pathological appearance. However, there are major variances in the genetic and physiological makeup of different cancers, which in turn requires the development of specific treatment options. Biomedical imaging, especially with PET, is one method that can identify important differences in tumours, allowing clinicians to better understand the condition and prescribe a personalised patient management plan. At the same time, patients are becoming more medically literate, through easier access to information via the internet and the media. This is resulting in patients demanding the application of these new technologies in diagnosing and managing their condition, and requesting information about planning and managing their treatment. CRCBID is working to accelerate the development of new imaging technologies and systems that can use PET throughout the management of a patient’s condition.

Attention to detail

Providing improved diagnostic tools for individual patient management is what drives the use and development of PET/CT within clinical practice. PET/ CT is now available in many sites in Australia and as a combined tool offers the very best functional imaging technology in use today. The choice of treatment can be vastly improved simply by applying best diagnostic imaging characterisation.

For example, by mapping the extent of metabolic activity in cancers, the images derived from a PET/CT scan have been shown to provide a greater degree of precision to surgical planning and radiotherapy dose delivery than other imaging modalities such as CT or Magnetic Resonance Imaging (MRI).

PET/CT is a valuable tool for a range of oncology treatment tasks:

• Detection of cancer


• Characterisation of known masses


• Staging/restaging of proven cancer


• Radiotherapy planning


• Monitoring of treatment

CRC for Biomedical Imaging Development (CRCBID) works with practising clinicians, industry and research partners to develop high specificity imaging radiopharmaceuticals for PET and high-sensitivity detectors for medical and industrial imaging applications.

Assisting clinicians to detect, diagnose and manage treatment of diseases earlier, through the development of more sensitive and specific disease markers, is the underlying goal of CRCBID.

It is also fostering the growth of Australian expertise in biomedical imaging and building the nation’s capacity to serve the needs of researchers, clinicians and industry people working in this field.

CRCBID is a leading edge Australian research company established and supported under the Australian government’s Cooperative Research Centres program. Visit www.crc.gov.au for further information.