Radiation and Radiotherapy
Confused about radiation and radiation therapy?
Here is everything you need to know from elements to isotopes and how radiation is used in medicine.
What Makes an Element?
The universe is made of elements, whether it’s the carbon that makes up your body, the oxygen we breathe, or the copper in your phone. Atoms are the smallest unit of any element, and every atom is made of the same three components: positively charged protons, neutrally charged neutrons, and negatively charged electrons. Protons and neutrons bind together to form the nucleus at the center of any atom, and electrons exist in the space around these nuclei. But, if they all use the same components, how do we get different elements?
Elements are defined only by the number of protons found in the nucleus, so every hydrogen atom has exactly one proton, every helium atom has exactly two, every lithium atom has exactly three, and so on. Protons need electrons to balance out their positive charge. So if a carbon atom has six protons, then it will need six electrons to be stable. These electrons exist around the nucleus balancing out the proton's charge so that no atom is too positive or too negative. The behavior of electrons is what we call chemistry, and they are what define chemical stability.
However, like magnets, protons are constantly repelling each other inside the nucleus due to their charge—which makes for quite the awkward party. So, neutrons are also present in the nucleus to keep all the protons comfortable by giving them the space they want. Every nucleus has a number of neutrons that it likes to have to be stable. Hydrogen atoms tend to have no neutrons, helium atoms tend to have two neutrons, bromine atoms are fine with 44 or 46 neutrons. These numbers are essentially random, and we only know what number of neutrons each element likes by measuring them. The behaviour of protons and neutrons in a nucleus is what we call nuclear physics, and they are what define nuclear stability.
Isotopes and Stability
As mentioned earlier, only the number of protons defines an element, so the atom of any element can actually have any number of neutrons in its nucleus. But remember, only a small number of these possibilities exist in nature.
We call these different nuclear configurations ‘isotopes,’ and we identify them by the total mass of their nucleus. For example, hydrogen-1 has one proton and no neutrons, hydrogen-2 has one proton and one neutron, and hydrogen-3 has one proton and two neutrons. Some elements have a few stable isotopes, some only have one, and some have zero stable isotopes. Unstable isotopes are what we consider ‘radioactive,’ and we call them ‘radioisotopes.’
The simplest example is hydrogen. Hydrogen usually has no neutrons, and so hydrogen-1 is the most common isotope for hydrogen; it, along with Hydrogen-2, are the only stable isotopes for hydrogen. Hydrogen-3 is a radioisotope that decays over time; it is not stable and will gradually disappear.
Unstable to Stable,
The Nature of Radioactivity
What does it mean to be unstable? Instability, in the simplest terms, refers to having a high energy state. Scientists, like anxious parents, call anything with too much energy unstable, always worrying about where that energy is going to end up.
Similarly, stability refers to a low energy state, and everything in the universe wants to be in as low an energy state as possible. Stable isotopes are relaxed; having no excess energy to lose, so they don’t do anything interesting. In contrast, unstable isotopes are simply atomic nuclei with too much energy, and they want to release that extra energy they have to enter a lower and more stable energy state. But how can an atom release this extra energy?
By any means necessary! All radiation is just atoms ejecting their excess energy into their surroundings. These nuclear processes happen near instantaneously, releasing a lot of energy from the nucleus; we call this nuclear decay. This high energy can cause damage to its surroundings and is what makes radiation dangerous. Once a nucleus has undergone decay, its energy is spent and it has a new, more stable nuclear configuration of protons and neutrons. This often transforms the atom to a different element because many decay processes involve the increase or decrease of the number of protons in the nucleus.
No One Way to Decay
As you can imagine, different radioisotopes release different amounts and types of energy depending on their specific energy states and available decay pathways. Some decay processes release very high, dangerous rates of radiation, and some are safe enough to hold in your hands. But like all hazardous materials, the dose makes the poison. Radiation already exists everywhere around us, from bananas to medical X-rays—even a small fraction of all the carbon isotopes in your body are radioactive!
Some isotopes are sluggish and decay over time periods longer than the age of the universe, and some particularly angry isotopes don’t even last long enough to be observed. We measure the rate of decay using half-life, which is the amount of time it takes for half the material to disappear. So, a longer half-life means that decay is slower.
The different forms radiation can take are many, and all have unique and interesting properties. The most common and relevant types are α, β, γ, and Auger radiation. Radioisotopes that emit radiation on the electromagnetic spectrum, like γ emitters, can be used for imaging and diagnosis. Radioisotopes that emit other particles, like β- or α emitters are commonly used for therapeutic approaches. Interestingly, most radioisotopes emit more than one type of radiation, making some useful for both diagnostic and therapeutic approaches, and we call the combination of the two theranostics!
Types of Radiation
Not all radiation is dangerous; in fact most radiation is actually completely harmless. For example, the light our eyes detect to see the world around us is actually a form of electromagnetic radiation. We can actually only see a small fraction of the electromagnetic spectrum. The microwaves we use to heat our food, radio waves we use for Wi-Fi and communication, and the visible light we use to see are all low energy forms of electromagnetic radiation, and all are completely harmless! These are all examples of non-ionizing radiation.
What you have to worry about is Ionizing radiation, which is radiation that has enough energy to knock electrons off of atoms and make them chemically unstable or break chemical bonds. This is mostly an issue because we are made of chemicals—just like everything else. Ionizing radiation is what most people mean when they talk about radiation, and it is the kind of radiation produced by nuclear decay. This ionizing radiation is what we use for medical imaging and therapy, and the unique properties of the different types of ionizing radiation allows for many new opportunities for patients.
Meet the Family:
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The combination of two protons and two neutrons is what makes up an α particle. This combination is actually identical to the Helium-4 atom, but with the absence of its electrons. This makes α particles highly chemically unstable allowing them to rip electrons from anything nearby. These particles are also ejected from radioisotopes with high velocity; combined with their weight, this gives them very high kinetic energy. This destructive combination is what makes α particles particularly hazardous, but what they have in power, they lack in range. They will deposit all their energy over very short distances. Much like a cannonball, they can break through just about anything, but they won’t go much farther than that. All you need to protect yourself from an α particle is a sheet of paper!
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Beta emitters fall into two categories: β- emitters used for therapy, and β+ emitters used for imaging.
β- : A β- particle is actually just an electron, the only distinction is that β- particles are the product of nuclear decay. These particles are fired from the nucleus with very high energy, like bullets from a sniper rifle. And like sniper rounds, these particles have a very long range and can pass straight through multiple cells depositing a fraction of its energy into each. Because β- particles spread their energy over long distances, individual cells actually receive little direct damage, but the long range allows for effective coverage of diseased tissues.
β+ : β+ emitters are a very unique category of radioisotopes because they produce positrons, which are a type of antimatter! Specifically, a positron is the antimatter counterpart of an electron. When matter and antimatter particles collide, they destroy each other in an event called ‘annihilation.’ Because electrons are so abundant everywhere in the universe, positrons usually only get to live for an incredibly short amount of time before finding an electron. When this happens, the annihilation event produces two identical γ-rays moving in opposite directions, and these γ-rays always have an exact energy of 511 keV. This incredibly unique signal can be seen with special detectors used for Positron Emission Tomography (PET), an incredibly powerful tool for 3D disease imaging.
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Most radioisotopes produce high energy electromagnetic radiation, which again is just the fancy name for light! Gamma rays are different from visible light in that they exist far off of the part of the electromagnetic spectrum we can see. These light rays are so high energy that most of the time they just pass straight through the body doing little damage. Because of this, we can use specially designed detectors that can see this light and use it to produce an image, just like a camera!
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An Auger emission is a very low energy electron that is ejected from an atom. These emitters are another unique type of radioisotope because Auger emission is actually not a nuclear process. These electrons are the same electrons that surround the nucleus. If an electron is given enough energy, it can ‘jump’ out of the atom. This can allow for another electron to ‘fall’ into the place of the previous electron, and when that electron ‘falls’ to a lower energy state, it will release more energy. This energy can allow another electron to ‘jump’ out, and you may very quickly see the pattern here. Auger radioisotopes are isotopes that undergo radioactive decay processes that result in the loss of an electron from the atom, this leads to the above cascade often resulting in the ejection of many Auger electrons. These electrons have incredibly low range, only being able to cause damage to structures in their immediate vicinity, but they can deposit a lot of energy. These isotopes behave exactly like shotguns, producing multiple, highly destructive emissions over very short range, and because of the loss of many electrons, the resulting atom is an incredibly chemically unstable product that can do further damage to structures in the vicinity. But, often, Auger emitters aren’t in range of anything important, so they are usually not that lethal to cells.
Radiation & Radioligands,
A New Approach to Medicine
Radiopharmaceuticals are just like normal pharmaceutical drugs, the only difference is that they are radioactive! These radiopharmaceuticals all generally follow the same formula. First, you have to find a chemical that targets the disease you are treating. For example, if you are looking to treat cancer, you want a chemical that naturally goes to cancer cells. Then, all you do is attach a radioisotope to that chemical. Depending on what you want, you can attach different isotopes; for example, if you wanted to image the site of disease for diagnosis or track patient progress, you could attach a β+ or γ emitter, or if you wanted to perform therapy, you could attach an α-emitter or β- emitter to kill the diseased cells.
Radiopharmaceuticals allow for a completely new and unique approach to medical diagnosis, and treatment circumvents many of the challenges faced by traditional medicine. Where these medicines have shone the brightest is in the field of medical imaging. Because radioactive materials are constantly emitting radiation, we can use special detectors to track exactly where they are in the body at any time. This is particularly advantageous because it can completely eliminate the most challenging part of imaging: finding what you are looking for! Radioactive tracers automatically go to the site of disease, and the emitted radiation acts like a flare gun telling doctors exactly where to look. In this way, only the site of disease is visible, leaving out anything that would end up confusing even the most experienced radiologists. We call such techniques to visualize only points of interest ‘functional imaging.’
But wait, isn’t all of this stuff radioactive? How is it safe? Yes, radiation is dangerous, but just like any other substance, the dose makes the poison. All drugs to an extent are poisons, and some are incredibly potent poisons that could kill you much faster than radiation ever could, but we acknowledge medicines' ability to save lives and accept the associated risks. These risks are minimized because we have incredibly strict policies on these substances, and we understand appropriate dosing limits. Radiation is the same; it has negative effects that we know very well, and with strict regulation these hazards are minimized. This is how it is safe for doctors and scientists to handle and prepare radioactive drugs every day, and why they are safe to give to patients as they need them, allowing them new and exciting opportunities!