What is the PET?

When the doctor suggests that you have a PET scan, it doesn't sound strange to us. We may be a little afraid of the diagnosis that will be derived from the test, but we have become accustomed to these acronyms belonging to the hospital environment. PET stands for nothing less than positron emission tomography and is a technique that involves many branches of science such as mathematics, physics, chemistry, biology, biochemistry, pharmacy, and, of course, medicine.

This technique has enabled progress in such sensitive fields of medicine as oncology (detection of tumours), neurology (diagnosis of diseases such as Alzheimer's or Parkinson's, and brain tumours), and cardiology (distinguishing between healthy tissue and infarcted heart tissue).

In addition, this medical technique has advantages over others such as CT (computerized axial tomography) or MRI, as it allows the detection of metabolic alterations, which are before the anatomical changes (detected by CT or MRI) and thus allows an early diagnosis of the disease.

Positrons are the anti-particle of the electron, i.e. they have the same mass and opposite charge to the electron. Their existence was predicted by Dirac, and C. D. Anderson was the first to detect them in gamma radiation. What makes them so interesting for PET is that for each collision with an electron, two photons are generated, and this allows (along with everything else that we will explain slowly) the sensitivity of this technique. To use PET, we therefore need to generate positrons, and this is achieved using a cyclotron. This apparatus was invented by E.O. Lawrence and M.S. Livingston to accelerate particles. The high kinetic energy generated can be used in nuclear reactions to obtain the positron-emitting radionuclides, which are used in PET.

In the cyclotron, particles move inside two semicircular metal vessels that are contained in a vacuum chamber within a magnetic field provided by an electromagnet. In today's cyclotrons, accelerating ions is preferred. In particular, 18F is often used as a radionuclide, which is generated in the nuclear reaction: 18º + proton → 19F → 18F + neutron, and is known as the proton-neutron (p,n) nuclear reaction.

More technically, what is done is to accelerate hydride ions that have been generated in an ion source at the centre of the magnetic field, and once they leave the magnetic field, pass them through thin sheets of carbon that strip the electrons from these negative ions, generating protons. This beam of protons is then passed through collimators and is incident on the target: where the nuclear reaction takes place.

So much for the physics part, now we come to the chemistry (and pharmacy) that deals with the design of the so-called radiopharmaceuticals or antimetabolites: they are composed of a molecule analogous to any with metabolic activity in the human (or animal) body and a positron-emitting radionuclide, such as 18F or 11C, 13N, 15O, which are considered biological tracers and have a half-life of 110, 20, 10 and 2 minutes, respectively. The most commonly used is the first one since, as it has a lower emission energy, it has a positive effect on the resolution of the images obtained. In addition, no gamma rays are emitted during their decay, which could interfere with the detection of gamma photons resulting from electron-positron annihilation. The most commonly used molecule in diagnostic PET is 2-[18F]-fluoro-2-deoxy-D-glucose (FDG).

The patient receives the radiopharmaceutical intravenously and must remain at rest to allow the drug to be incorporated into the body, and then the PET scan is performed. It has the advantage of having a short half-life, so the patient is not exposed for a long time to radiation, which is in any case not dangerous, and PET is a non-invasive diagnostic technique.

Inside the human body, to increase its stability, the radionuclide emits positrons, which move a distance proportional to the emission energy and which, on colliding with an electron, generate two photons, following Einstein's well-known equation of E=mc2, which are emitted at 180º concerning each other.

For example, applied to oncology (and here we are getting into human biology and biochemistry): in PET-[18F]-FDG studies, an increase in the glycolysis of tumour cells is observed. In other words, glucose metabolism and lactate production are increased while oxidative pathways are reduced. As this radionuclide is a glucose analogue, it enters the cell membrane using the same transporters as glucose (GLUT) and is then phosphorylated to [18F]-FDG-6-phosphate by the enzyme hexokinase. But this metabolite is no longer a substrate for downstream enzymes and consequently is captured and accumulates inside the cell, being proportional to glucose metabolism.

The PET scanner allows the detection of photons using ring-shaped detector blocks, which surround the patient (360°) and are made of photomultiplier tubes with germanium and potassium oxide crystals. The signal obtained is collected at the anode. And this requires mathematics: in 1979, Godfrey Hounsfield and Alan Cormack were awarded the Nobel Prize in medicine for their work on the development of computed tomography.