On Positron Emission Tomography and Proton Therapy

1. Introduction

Positron emission tomography (PET) and proton therapy (PT) are two major medical techniques. The former technique is used for diagnostics in oncology, neurology, psychiatry and cardiology, and the latter one for therapy in oncology. Most of the diseases they are applied to appear dominantly in older persons. Hence, these techniques play special roles in lengthening the life cycle and improving its quality.
Both PET and PT are performed with proton beams from accelerators. In the former case, the accelerator is a small cyclotron, and the proton beam is employed for producton of substances enabling one to detect diseases. In the latter case, the accelerator is a large cyclotron or synchrotron, and the proton beam is employed directly for treating tumours.

2. On Positron Emission Tomography

2.1 What Is Positron Emission Tomography?

PET is a medical diagnostic technique that gives very precise three-dimensional images of vital processes and functions of tissues, organs, parts of the body and the whole body1.Therefore, these images are called physiological or functional images. In order to obtain such an image, one has to introduce in the body, usually in the bloodstream, a substance made up of specific biological molecules in which certain short-lived radionuclides have been chemically incorporated. Radionuclides are radioactive atoms, i.e., atoms whose nuclei are unstable and decay by emitting radiation. The radionuclides in question here are the ones decaying by emitting positrons, which are positively charged particles that are the antimatter counterparts of electrons. The above mentioned method of chemical incorporation is called labelling, and the resulting substance is called radiotracer or, when it is approved for clinical use, radiopharmaceutical. The specficity of its molecules is in their active participation in metabolic processes in the body. When introduced in the body, they are accumulated mostly in tissues having high metabolic activity. The typical time needed for the accumulation is about one hour. Upon this, the patient is placed in the scanner.
The radiopharmaceutical that is mostly used for PET is fluorodeoxyglucose (FDG), whose molecules contain radionuclides flourine-18, whose life-time is about 110 minutes. The other typical radionuclides used for PET are carbon-11, nitrogen-13 and oxygen-15, whose life-times are about 20, 10 and 2 minutes, respectively. It is clear that, due to their short life-times, their production center must be close to the clinical center in which they are used.

2.2 What Are Single Photon Emission Tomography, Ultrasound Imaging, Computed Tomography and Magnetic Resonance Imaging?

Single photon emission tomography (SPET) is a functional diagnostic technique similar to PET that is based on the use of radionuclides decaying by emitting photons rather than positrons. Photons are quanta of electromagnetic radiation. This technique is less accurate and less costly than PET. On the other hand, ultrasound imaging (USI), computed tomography (CT) and magnetic resonance imaging (MRI) are medical diagnostic techniques that give anatomical or structural images of tissues, organs, parts of the body and the whole body. USI is based on reflection of high energy sound waves from tissues, CT on absorption of low energy X-rays in tissues, and MRI on perturbation of aligned magnetic moments of atomic nuclei in tissues with radiofrequency waves. In most cases, PET gives images that are superior to those obtained by USI, CT and MRI. But, a PET scan is more expensive than an USI, CT or MRI scan.
Today, there are scanners providing PET and CT in the same session, immediately one after the other, with the patient not changing the position between the two scans2. They are called PET/CT scanners. Such a scanner enables one to obtain and fuse functional and structural images, and analyze these two complementary sets of data simultaneously.

2.3 How Is Positron Emission Tomography Performed?

After traveling up to a few millimeters through the tissue, a positron emitted from a radionuclide encounters an electron, belonging to a molecule of the tissue, and they annihilate each other3. As a result, two photons appear at the point of annihilation moving in the opposite directions. Since the distances the photons pass to the detector ring of the scanner, located around the patient, are approximately the same, they are detected almost coincidently. The photons that do not reach the opposite sides of the detector ring in almost coincident pairs are ignored. This means that only the pairs of photons appearing due to annihilation of the emitted positrons and the electrons they encounter are taken into account. For each pair of photons that reach a pair of detectors at the opposite sides of the detector ring it is possible to determine very precisely the coordinates of the point in the body they originate from, i.e., the corresponding point of annihilation of the positron and electron. This point belongs to the volume of the tissue under investigation, where the radiopharmaceutical accumulates. Determination of the coordinates of a very large number of such points enables one to produce a very accurate functional image of the tissue. This is achieved by a complex calculative procedure. The obtained image is interpreted by a physician specialized in nuclear medicine, creating the basis for the diagnosis and subsequent treatment of the patient.
An early PET scanner had only one detector ring, and collecting the data and generating the image of the tissue under investigation was restricted to only one transverse plane. The resulting image was two-dimensional. The three-dimensional image was generated by moving the patient through the detector ring. It was a sequence of two-dimensional images. A modern PET scanner has several detector rings placed one after the other, forming a detector cylinder. It enables one to generate a three-dimensional image of the tissue much faster than with a scanner with only one detector ring.
The short-lived radionuclides to be used for PET are produced with small cyclotrons giving proton beams of the energy of around 15 MeV. Protons are nuclei of hydrogen atoms. A production center of radiopharmaceuticals labeled with these radionuclides contains such a cyclotron, and a radiochemical laboratory, for production and quality control of these radiopharmaceuticals. Radiopharmaceuticals labeled with radionuclide flourine-18 can be used in the clinical center associated with the production center and in the other clinical centers that are close to it. The half-life of fluorine-18 (about 110 minutes) determines the longest time one can use to transport these radiopharmaceuticals to the other clinical centers, being about two hours. Radiopharmaceuticals labeled with radionuclides carbon 11, nitrogen-13 and oxygen-15 can be used only in the clinical center associated with the production center.
Today, the useful space in a typical clinical and production PET center has the area of about 2,000 m2. The total costs of establishing such a center containing one PET/CT scanner are about EUR 8.5 million. Its operation and maintenance requires the staff of about 20 members, including two physicians specialized in nuclear medicine and radiology, one medical physicist, two radiochemists, one pharmacist and one microbiologist. The average time needed for one scan is about one hour. If the scanner is used eight hours per day and 220 days per year, the total number of treated patients can be 1,760 per year. However, in practice, the total number of patients treated is such a center is about 1,250 per year.
PET is a non-invasive medical diagnostic technique, but it involves deposition of certain radiation dose in the body4. However, the radionuclides in question are short-lived, and the deposited radiation dose is only about 7 mSv. It should be compared to the radiation dose deposited during an X-ray scan of chest — about 0.02 mSv, the radiation dose deposited during a CT scan of chest — about 8 mSv, and the average background radiation dose per year — about 2 mSv.

Nebojša Nešković: Vinča Institute of Nuclear Sciences, Belgrade, Serbia.
1 Phelps, M.E., Hoffman, E.J., Mullani, N.A. and Ter-Pogossian, M.M. (1975): “Application of Annihilation Coincidence Detection To Transaxial Reconstruction Tomography”, Journal of Nuclear Medicine, No. 16, p. 210.
2 Beyer, T. and Townsend, D.W. (2006): “Putting ‘Clear’ into Nuclear Medicine: A Decade of Pet/ct Development”, European Journal of Nuclear Medicine and Molecular Imaging, No. 33, p. 857.
3 Zanzonico, P. (2004): “Positron Emission Tomography: A Review of Basic Principles, Scanner Design and Performance, and Current Systems”, Seminars in Nuclear Medicine, XXXIV, p. 87.
4 Wu, T-H., et al. (2004): “Radiation Exposure During Transmission Measurements: Comparison Between Ct- and Germanium-based Techniques with a Current Pet Scanner”, European Journal of Nuclear Medicine and Molecular Imaging, 31, 38.

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