Positron emission tomography (PET)

What is it

Positron emission tomography (PET) is a diagnostic test that is part of the field of nuclear medicine.

In nuclear medicine, compounds called radiopharmaceuticals are used for diagnostic or therapeutic purposes: they consist of a substance with biological functions and a particular type of radioactive atom, called radionuclide and can be administered by injection, orally, locally or through the peritoneum.

The biologically active part has the property of localizing itself at the level of the tissues conveying in them the radionuclide to which it is combined. The radionuclides used are unstable isotopes of the chosen atoms, which tend to transform rapidly through a process called decay, during which they emit radiation.

In PET this radiation is picked up from the outside by special scanning equipment and translated into diagnostic images.

When a radiopharmaceutical is administered for the execution of PET, the attached radionuclide has the function of making visible the characteristics and the state of activity of the tissues in which the radiopharmaceutical is located.

Unlike ultrasound, computed axial tomography (CT, or more simply CT) and nuclear magnetic resonance imaging (MRI) – imaging methods that make visible the structural characteristics of tissues and organs and therefore provide morphological information – PET gives functional information (similarly to what happens with scintigraphy, but different on a technical level).

In disease processes, PET scans can detect alterations in biological functions that accompany or sometimes precede anatomical changes found with CT or MRI.

How radiopharmaceutical works

The compound most used today in positron emission tomography as a radiopharmaceutical is fluorodeoxyglucose, indicated by the chemical abbreviation 18F-FDG: it is a sugar similar to glucose, associated with a radioactive isotope of fluorine (18F).

As similar to glucose, which is an essential and ubiquitous substrate of the cellular metabolic processes that are constantly occurring in the human body, 18F-FDG is also incorporated by cells, but is not fully metabolized as long as its isotope 18F continues to emit radiation.

During the radioactive decay phase, the isotope 18F generates particles called positrons.

Positrons are positively charged subatomic particles that meet with negatively charged electrons and annihilate themselves through a process called annihilation, which transforms the mass of particles into radiation in the form of gamma photons.

In a technically simpler variant of PET, called single-photon emission computed tomography and indicated by the abbreviation SPECT, radioisotopes are used that do not emit positrons, but directly gamma radiation.

The duration of radioactivity of a radiopharmaceutical depends on a typical parameter of each isotope called half-life, or half-life, which corresponds to the time it takes for half of the atoms of an isotope sample to decay, that is, to spontaneously transform into another element. The more unstable the isotope, the shorter its half-life: in the case of 18F this period is about 110 minutes.

During the decay process of its radioactive component, the fluorodeoxyglucose molecule incorporated in the cell therefore remains “visible” to the PET scanner, practically assuming the role of “tracer” of its metabolic situation of the moment.

From oncology to neurology: what is PET for

Positron emission tomography performed with fluorodeoxyglucose, referred to in short as PET 18F-FDG, is able to visualize the current physiological processes of the explored tissues and thus reveal their variations compared to normal conditions.

For these reasons, its applications are manifold.

For example, in the case of neoplasms, PET 18F-FDG can show an abnormal activation of metabolic processes in populations of tumor cells in the proliferation phase, since these tend to assimilate fluorodeoxyglucose at a rate higher than normal.

In oncology, the examination is therefore used in order to:

• characterize the functioning of primary neoplastic lesions, relapses and metastases;
• define the staging (i.e. the spread and degree of malignancy) of the disease;
• verify its evolution during treatment with chemotherapy or radiotherapy.

Therefore, it is now the main diagnostic tool for the identification, differential diagnosis and monitoring of a wide variety of cancers (lung, colorectal, head and neck, breast, ovary, lymphoma, melanoma, etc.).

In addition, PET 18F-FDG plays a fundamental role in neurology, where it is used in the diagnostic investigation of neurodegenerative diseases (Parkinson’s disease, amyotrophic lateral sclerosis, etc.) – including the various forms of dementia (Alzheimer’s disease, vascular dementia, etc.) – and in the standard pre-surgical evaluation of patients with epilepsy.

Diagnostic imaging performed by the administration of radiolabeled glucose is particularly effective in the diagnosis of dementias, since glucose is the only energy substrate used by nervous tissue. By observing the distribution of 18F-FDG in brain tissue, in fact, it is possible to detect its metabolic activities and thus find the possible presence of losses at both molecular and synaptic level in specific areas, commonly associated with various forms of dementia.

In the diagnosis of Parkinson’s disease and other parkinsonisms (such as, for example, multiple system atrophy and Lewy body dementia), however, the use of SPECT is still preferred. This technology, in fact, although less sophisticated than PET, is more effective in the diagnosis of these degenerative diseases, since it allows to detect one of their distinctive features, namely the loss of presynaptic dopamine transporters.

In cardiology, the uptake of 18F-FDG is able to represent with extreme precision the residual areas of vital myocardial tissue in case of coronary artery disease or after heart attack (in this case we speak of myocardial PET).

But PET 18F-FDG is also applied in other specialist areas, for example in the study of a number of rheumatic diseases, immunological disorders and infectious diseases.

Finally, with the use of radioactive tracers other than 18F-FDG it is possible to explore, as an alternative to glucose metabolism, other physiological phenomena indicative of ongoing pathological processes, such as:

• alterations in neurotransmission or specific degenerative phenomena in particular areas of the brain;
• changes in blood circulation in tissues affected by ischemia, hemorrhage, atherosclerosis.

In the first case, for example, radiopharmaceuticals are used that are selectively picked up by the dopaminergic system in the brain structures affected by Parkinson’s disease or that make visible the deposits of beta-amyloid substance typical of Alzheimer’s disease; in the second case, so-called “perfusion tracers” are used to highlight the state of blood circulation in the organs studied, for example in the walls of the heart, with the PET scan.

In oncology, in addition to fluorodeoxyglucose, choline labeled with carbon or radioactive fluorine (11C- and 18F-choline) is used as a radiopharmaceutical, a substance that accumulates selectively in slow-growing neoplastic cells and is particularly suitable for the evaluation of some tumors such as prostate and liver cancer.

In summary, the measurement by PET scanning of the uptake (which can be increased or decreased depending on the pathological process) and the diffusion in a tissue of a particular radiopharmaceutical, chosen according to the diagnostic objectives, provides a precise image of the functional state of that tissue.

PET, CT or MRI?

In general, PET can allow to diagnose a pathological process before CT and MRI, as functional alterations often precede changes in the structure and morphology of the affected tissues. Today, however, these tests, and in particular CT and PET scans, are increasingly used in combination.

The PET-CT tomograph is a device in which the PET and CT detection systems are assembled and controlled by a single control console, so as to allow the radiologist to integrate the morphological images of the CT scan with the functional ones of the PET.

The combination of the two exams in real time leads to an improvement in the resolution and contrast of the images obtained, thus making the identification and delimitation of the studied areas more accurate, and a reduction in the time of execution of the exam.

Due to its effectiveness in the early diagnosis of pathological processes, PET can take on value in secondary prevention, increasing the chances of cure and control of the disease in progress. However, it should be remembered that, like other diagnostic investigations, it must be performed in the presence of a concrete diagnostic suspicion or in selected cases that present a risk of disease higher than that of the normal population. Since it is a procedure that exposes to radiation, its use is in fact envisaged on the basis of well-defined clinical indications.

How the exam takes place

The PET or PET-CT examination is carried out at the radiology and nuclear medicine unit of a health facility, without the need for hospitalization.

The requirements to be followed in the preparation phase are simple:

• observe fasting for food and drink (with the exception of water) in the previous 6 hours (in the case of PET with FDG limit sugars and carbohydrates even in the previous day);
• avoid cigarette smoking and consumption of alcohol, caffeine or other stimulants in the previous 24 hours;
• Refrain from strenuous physical activity in the vicinity of the exam.

With regard to the intake of usual medicines, it is advisable to inform the doctor in advance of the current therapy and follow his indications. It is also very important to report in advance the possible presence of diagnosed pathologies (possibly providing the relative documentation), a state of pregnancy (certain or presumed) or breastfeeding, to facilitate the doctor in interpreting the result.

Although the injected “radioactive” substance is an analogue of glucose, there are no contraindications to the administration of this test in patients with diabetes.

To perform the investigation, in fact, a small amount of radiolabeled glucose is sufficient which, as such, is not able to alter the patient’s glycemic balance. The latter, however, must regularly check his glycemic index in the days before the exam and postpone the booking of the exam, if this is too high.

The PET scan is non-invasive and the only risks are linked, as in the case of the CT scan, to exposure to ionizing radiation: it is therefore absolutely contraindicated during pregnancy, while in new mothers breastfeeding this must be interrupted after the examination for a period, which will be indicated by the doctor, sufficient to guarantee the total elimination from the body of the administered radiopharmaceutical.

The examination begins with intravenous administration of the radioactive tracer. After a waiting period that allows the substance to spread into the tissues through the bloodstream and once all metal objects (such as necklaces, earrings and the like) have been removed, you are placed in a supine position on the tomograph bed and asked to remain motionless for the duration of the scan.

The PET scanning device records the radiation emitted by the radiopharmaceutical from inside the body (but does not bring additional radiation from the outside) and a computerized system translates them into images that will then be reported by the nuclear medicine specialist.

The scan itself can take 20-30 minutes, while the whole procedure can take 2-3 hours. At the end of the exam you are discharged being able to resume all normal activities, including driving, and usual nutrition, and it is recommended to take plenty of water to favor the elimination of the tracer.

Those who have undergone PET and therefore temporarily retain some radioactivity, albeit at a low dose, are always advised not to stay near pregnant women and children for a few hours.