Application of Gamma Rays in Medicine

RADIOTHERAPY

Introduction

Nuclear and isotope techniques are widely used in numerous areas of human activity and for more than century have prominent application in different areas including medicine. This paper focuses on radiotherapy which is one of the applications of gamma rays in medicine.

To start with, a brief understanding of gamma rays should be known first, including properties and sources of gamma rays. Without an understanding of gamma rays, the working principle of radiotherapy could not be demonstrated clearly.

An introduction of radiotherapy is then followed before I go into the details of the two main approaches in radiotherapy: external beam radiation therapy and brachytherapy.

Brief Ideas of Gamma RaysBoth gamma radiation and X-rays are highly penetrating EM waves. But gamma radiation has higher frequencies and energy. It is more dangerous than X-rays. Each gamma ray is a photon that is emitted from the nucleus of an atom when the nucleus comes down from an excited state that results from some kind of decay event. Gamma rays are similar to x-rays, in that they are still photons, but x-rays come from a similar step down in the electron cloud (Gilmore, 2008).

Properties of Gamma Rays

1. High frequency EM waves2. No charge3. Very weak ionizing power4. Very high penetrating power, never fully absorbed, halved by 25-mm lead5. Range in air is over 100m6. No defection in electric and magnetic field7. Detectors:a. Photographic filmb. Diffusion cloud chamber (scattered and hardly seen tracks)c. G-M counterSources of Gamma Rays

Gamma rays can be sorted into two categories by their sources, namely terrestrial gamma rays and cosmic gamma rays. The former are those generated on Earth while the latter are those produced by nuclear fusion reactions that occur within the core of stars, like the sun. However, we can only observe terrestrial gamma rays here because cosmic gamma rays are absorbed by the ozone layer before reaching the surface of Earth. The only way to detect cosmic gamma rays is to launch a satellite-observatory into space.

Radiotherapy

Radiation therapy is the treatment modality of malignant and benign diseases, by means of ionizing radiation. Since a wide spectrum of ionizing radiation is known nowadays, available technological solutions which use these sources of radiation, are also numerous. There are two major approaches in radiation therapy: external beam radiation therapy (also known as teletherapy), where the ionizing radiation comes from external source outside the body of the patient, and brachytherapy, where the source of radiation is placed inside the patient, inside the tumor, or in its close proximity.

The use of radionuclides in the treatment of diseases is long more than a century, starting with observation of P. Curie that a radium source in direct contact with skin causes burns. The first application of radium-226, as sealed sources in radiotherapy occurred in 1915, but this method was abounded in the middle of the twentieth century, when reactor isotopes (as cobalt) remote manipulation became available (Magill, 2005). One of the most important applications of radionuclides in radiotherapy is based on the use of sealed radiation sources for external beam therapy, the use of implants for the treatment of prostate cancer, intravascular radiotherapy and use of radiopharmaceuticals for therapeutic purposes. In addition to these methods, rapid development and implementation of a wide range of new and effective techniques, such as radioimmunotherapy and ion beams is expected in near future (John, 1983).External Beam RadiotherapyIn external beam radiotherapy, where radiation is delivered from outside the body, photon energies of millions of electron volts are required to penetrate the tissue and reach the tumors inside the body. This technique has been applied to patients just after the invention of x-rays, by kilovoltage x-ray units (Podgorsak, 2006). Immensely rapid development of high energy gamma and x- ray treatment started by introduction of cobalt-60 teletherapy in the 1950s and soon after with construction and development of first medical linear accelerators. In addition to x-ray megavoltage modality, linear accelerators are capable to provide electron beam treatments, both with a wide range of energies (Podgorsak, 2005). In countries where facilities for the maintenance of linear accelerators are lacking, cobalt therapy may be the most appropriate choice for radiotherapy.

In external beam radiotherapy, the dose of ionizing radiation is provided by radiation sources outside the body, using photons or electrons of energies of several MeV, which is sufficient for the penetration of radiation to tumor sites in the body. A source of radiation in external radiotherapy is mainly cobalt-60 or linear accelerators. Basic components of teletherapy machines are:

a) Gantry with stand, which houses the source of radiation and beam collimating system; b) Patient treatment table; and c) Control console in the radiotherapy control room.

The therapeutic beam at cobalt machines is produced continuously, by beta decay of radioactive source, placed in the gantry of the machine. The result of the beta decay is excited nuclei that emits gamma rays and achieves ground state.

Physical form of source is a metallic cylinder-shaped capsule with a length and diameter of 2 cm. The main features of radioisotopes used for clinical therapeutic beams are: high energy of emitted gamma radiation (energies of 1.17 MeV and 1.33 MeV), high specific activity, enabling production of small radiation sources (specific activity of 10 15 Bq/kg or higher) and relatively long half-life. The later property provides replacement periods of approximately 5 years that corresponds to one half-life.

Accurate dose delivery to the target volume is of the main interest of modern radiotherapy. During treatment, the therapeutic beam is shaped by the collimation system, to a size of 5 cm x 5 cm up to 35 cm x 35 cm, at the distance of 80 cm from the center of the source. Overall accuracy in tumor dose delivery is recommended by ICRU (Bikit, 2013) and should be within 5%, based on evaluation of errors in dose delivery in a clinical environment.

To ensure quality of treatment, acceptance test, commissioning, and calibration of a clinical beam must be performed at installation. This process provides information on radiation output of the machine, which is a dose rate at reference depth at certain point in a water phantom for a nominal source to skin distance and reference conditions (reference field size, reference temperature and air pressure, etc) (Podgorsak, 2005). Calibration of both electron and photon beams require an accurate dosimetric system, capable of measuring the dose deposited in a sensitive volume. The procedure for calibration of a clinical photon beam is recommended by a number of internationally recognized organizations as the American Association of Physicists in Medicine (AAPM), Institution of Physics and Engineering in Medicine and Biology (IPEMB) (UK), Deutsches Institut fr Normung (DIN) (Germany), Nederlandse Commissie voor Stralingsdosimetrie (NCS) and Nordic Association of Clinical Physics (NACP) (Scandinavia), or by international bodies such as the IAEA (Bikit, 2013). This procedure ensures accuracy and a high level of consistency in dose assessment in different radiotherapy centers.

Accuracy in dose delivery also requires careful treatment planning. This process is rather complex and involves numerous steps, consisting of beam characterization, patient data acquisition, generation of a treatment plan and transfer of the plan to the treatment machine, verification of a patient treatment plan and careful positioning of the patient at the treatment unit, and finally, treatment of the patient (Levitt, 2006). With modern computerized treatment planning systems that have advanced capabilities of beam shape generation, dose distribution calculation and minimization of dose to normal tissues, patient anatomy is represented as a 3D model based on CT slices generated during patient preparation. There are also other imaging modalities used in treatment planning, for better visualization of tumor tissues, in a process called image registration and fusion, such as MRI, PET, ultrasound, SPECT.BrachytherapyHundreds of thousands of patients each year is referred to brachytherapy treatments (in the Greek language brachys means close). In this technique, a sealed source of radiation is introduced into the body cavity or tissue and its proximity to the tumor, provides the necessary dose for the tumor and minimal dose to the surrounding healthy tissue. The radiation of radionuclides is usually of moderate energy gamma radiation, which allows homogeneous irradiation of the target and simultaneous protection of normal tissue. Radiation sources usually have a high specific activity and small size. With brachytherapy implants, it is possible to achieve successful treatment with very low energy photons (20 keV, palladium). Common sources include gamma-emitting radionuclides (iridium-192, cesium-137, iodine-125, palladium-103) whose radiation has a range of the order of cm in tissues. Shorter ranges, of order of mm, are achieved using beta-emitting radionuclides such as strontium-90, rhenium-188 and phosphorus-32 (Magill, 2005; Martin, 2006).

The first patient treatments were performed using radium sources (Levitt, 2006; Devlin, 2007). Development of nuclear physics and radionuclide production technology has leaded to significant increase in the number of radionuclides with features important for brachytherapy, such as half-life and type and energy of emitted radiation. Classification of brachytherapy modalities can be done using different criteria, such as technique used to load sources (manual, remote afterloading), period of implementation (temporary or permanent) or approach used to insert the source into the patient (interstitial, intracavitary, intraluminal or mold).The main features of brachytherapy source are: half-life, specific activity related to amount of radioactivity obtained for a certain mass of source and energy and type of radiation emitted from the source (energy spectrum). These characteristics determine the clinical application of the source.

Most of the radionuclides used in brachytherapy are of reactor origin. The radioactive isotope 137 Cs is a fission product (Joslin, 2001). The other isotopes are produced by neutron bombardment of stabile nuclei in a nuclear reactor (Joslin, 2001). The half-life of brachytherapy source ranges from few days to many years. The length of the half-life determines the period of source replacements. Of course, a longer half-life is more desirable, as it provides many patient treatments and thus reduces the cost of each treatment. The half-life is also important property for selecting the radionuclide for permanent and temporary implants. A shorter half-life is more desirable for permanent implants, as they remain presently in patients posing a certain risk of radiation exposure to the public and environment. The sources used for the permanent implantation are iodine, palladium and gold.

The strength of radioactive source used in brachytherapy is fairly limited by a specific activity. The specific activity defines the activity contained in the mass unit. Therefore, if the source has high specific activity, it is possible to design a brachytherapy source of small physical size, yet to be highly radioactive to provide efficient therapy. On the contrary, if the source has low specific activity, its use in brachytherapy is limited by its large physical size.

The average energy of the source is directly related to the number of photons penetrating the patient tissue. Higher energy sources allow deeper penetration in tissue and higher dose to larger distances. However, this also increases the shielding requirements for brachytherapy staff and environment. Therefore, low energy sources are commonly used in permanent implants. Due to the absorption of decay products in the patient itself, this technique does not imply significant radiation risk to the patients surrounding.

Cobalt and iridium are radiation sources commonly used in brachytherapy. The iridium has a spectrum with multiple energies of gamma radiation, however, significant contributions to the spectrum come from photons of energies 0.296 MeV (28.7%), 0.308 MeV (29.8%), 0.316 MeV (83.0%) and 0.468 MeV (47.7%)(Joslin, 2001).

Brachytherapy was been introduced over a hundred years ago (Joslin, 2001), and since then, many physical quantities have been used to describe the source quantitatively, i.e. to describe the source strength. Significant limitation of many of these quantities is related to the fact that the strength of source is assessed from the dose rate measurement around the encapsulated source placed in water or air. However, the dose distribution depends on a complex interaction processes in the source itself and its surrounding. Eventually, common quantities used for dose assessment in brachytherapy are:

Milligram-radium-equivalent (mgRaEq), where 1 mgRaEq of the radium substitute (source similar to radium-226) is defined as amount of the source that gives the same output as 1 mg radium source encapsulated in 0.5 mm platinum in the same output measurement geometry; Apparent activity (Ci): 1 Ci apparent activity of encapsulated radioactive source is defined as amount of encapsulated source that gives the same output, or exposure in air, as an unencapsulated source of the same isotope of 1 Ci activity; Air-kerma strenght (Sk): defined as the dose-free air along the transverse axis of an encapsulated source, measured at a large distance from the source such that the source can be approximated by a point source. Air-kerma strength has the unit of cGy cmh, and is represented by the symbol U (A.A.P.M., 1987). This is the internationally accepted physical quantity widely used in brachytherapy.

For the purpose of dose assessment, it is important to consider the physical size and shape of the radiation source. There are two approaches in which the source is treated either as a point source or more realistically, as a cylinder. The dose distribution around a point brachytherapy source decreases with the square of the distance (A.A.P.M., 1987). However, clinical sources have a finite size. The cylindrically shaped source is encapsulated in a metal shell of stainless still, platinum or titanium. In this case, suitable, more complex equations are used to calculate the dose around the line source as Sievert integral (Bikit, 2013) and TG43 formalism (Bikit, 2013). The principle of dose calculation in clinical application is based on superposition, i.e. the final dose distribution at a certain point around the multiple of sources lying in the brachytherapy applicator is obtained as a sum of doses to a particular point, coming from each source (Devlin, 2007).

Although manufacturers provide the information on source strength, it is mandatory to perform in-hospital calibration of a source and thus, verify the source straight. The calibration should be traceable to national or international standards. The in-hospital calibration is performed according to internationally recommended protocols, most often with the calibrated dosimetry system, which includes a calibrated well chamber and electrometer (A.A.P.M., 1987).

Conclusion

Radiotherapy is an excellent example for transfer of modern technologies and scientific knowledge in daily clinical practice. Based on various properties of nuclei and radiation, such as the interaction of radiation with matter, radiation detection, biological effects of radiation and static and dynamic nuclear properties (magnetic properties, stability, radioactive decay), application of gamma rays bring on a daily basis immense benefits in the diagnosis and treatment of disease and in the development of medical science.

References

1) American Association of Physicist in Medicine (A.A.P.M.). (1987). Specification of Brachytherapy Source Strength. A.A.P.M. Report 21. New York.2) Bikit, I. (2013). Gamma Rays: Technology, Applications and Health Implications. Nova Science Publishers, Inc.. 3) Devlin, P. (ed.). (2007). Brachytherapy: Applications and Technique. Lippincott Williams and Wilkins.4) Gilmore, G. R. (2008). Practical gamma-ray spectrometry. (2nd ed.). John Wiley and Sons Ltd.5) Johns, H. and Cunningham, J. (1983). The Physics of Radiology. (4th ed.). Springfield. Illinois6) Joslin, C. (ed.). (2001). Principles and Practice of Brachytherapy: Using Afterloading Systems. Hodder Arnold Publishers.7) Levitt, S.H.; Purdy, J.A.; Perez, C.A. and Vijaykumar, S. (2006). Technical Basis of radiation therapy. (4th ed.). Springer-Verlag. Heidelberg. Germany. p. 3 31.8) Magill, J. and Galy, J. (2005). Radioactivity, Radionuclides, Radiation. Springer-Verlag. Berlin Heidelberg and European Communities.9) Martin, B. (2006). Nuclear and Particle Physics. John Wiley and Sons Ltd.10) Podgorsak, E. (2005). Radiation oncology physics: a Handbook for teachers and students. I.A.E.A., Vienna.11) Podgorsak, E. (2006). Radiation physics for medical physicists. Springer Verlag. Berlin. Heildelberg.