Radiopharmaceutical Production

1. Radiopharmaceutical Production Cyclotron radionuclide production STOP

2. Cyclotrons produce radionuclides by bombarding nuclei with high energy charged particles Since we are usually using proton bombardment, we change the element and the product nuclei typically lie below the line of stability. As a result, the decay is typically by positron emission or electron capture. Radionuclides which decay by positron emission can be used for PET. Contents General Principles Nuclear reactions and target physics Beam heating and Density reduction Target Foils Practical Target design Radionuclide Production STOP

3. General Principles In a typical application, a cyclotron, is used to prepare a specific radioactive species through a particular nuclear reaction. For example, 18F is often prepared via a proton-induced (p,n) reaction on 18O enriched water. In theory the 18O could be in any physical state, liquid water being one convenient form. Some facilities use a different deuteron-induced reaction—a (d,α) reaction on 20Ne (neon); under usual conditions neon is present as a gas, and this would be a typical gaseous target. The exact nuclear reaction and the chemical form of the target material is one of the choices that have to be made in designing a cyclotron target. There are many other factors which must be considered and some of these are explained in the following information.

4. + + + + + + How are radioisotopes made with a particle accelerator The goal of cyclotron targetry is to produce a radionuclide. To do this one must get the target material into the beam, keep it there during the irradiation and to remove the product radionuclide from the target material quickly and efficiently. The specific design of the target is what allows one to achieve this goal. An accelerator shoots a particle at high energy The particle reacts with a nucleus to form a new radioisotope

5. Nuclear Reaction Cross Sections The particle which hits the nucleus can interact in several ways A ELASTIC SCATTERING • Nuclear elastic scattering • Nuclear inelastic scattering with or without nucleon emission + a A INELASTIC SCATTERING A a a + a B NUCLEAR REACTION 1 • Projectile absorption with or without nucleon emission. b + D b + c + NUCLEAR REACTION 2 Each of these processes has a certain probability of occurring

6. Types of Nuclear Reactions The radionuclides that can potentially be made from different nuclear reactions are shown in the following diagram. The first letter is the particle in and the letter after the comma is the particle(s) emitted by the excited nucleus. This template can be overlaid on a chart of the nuclides to get the products Nuclear Charge Nuclear Mass

7. Radionuclide Separation • After the radioactive product is formed, it must be isolated from the residual target material and then chemically reacted with appropriate molecules to form the desired radiolabeled end-product. Common chemical routes to production of this compound involve reactions of fluoride ion, F-, in liquid solutions, and the use of the liquid target is often reasonable for such applications. There are other preparation methods that involve bubbling fluorine gas (F2) through solutions of appropriate chemicals. The latter methods might favor use of a gaseous target from which the 18F2 could be more easily isolated. • The choice is governed in part by the reaction yield and the chemical process that follows.

8. Physical State of the Target • Besides the chemistry requirements imposed by the post-irradiation need to incorporate the product radionuclide into particular molecules, other considerations that affect the decision as to the physical state of the target include the following: • The atom density of the target species in the target material—e.g., a solid or liquid might provide higher atom densities than a gas and thus produce greater amounts of the desired product. • The cross section of the intended target atoms for the specific nuclear reaction of interest—e.g., a small cross section may require a higher target density, often favoring a solid or liquid target over a gas. • The preponderance of interfering species in the irradiated target—some target materials may contain nuclear species that produce undesired radioactive products that might be difficult to separate from the desired species, and such considerations can affect the type of target selected; similar considerations may also apply to stable target species that interfere with separation of the desired product. • The associated undesired radioactivity of the target  materials following irradiation—high radiation levels of some potential target materials, as a consequence of incidental irradiation of miscellaneous species may mitigate against selection of some target types and/or favor selection of other types.

9. Power deposited > 1 kwatt Nuclear Reactions and Target Physics There are several factors which are related to the physics that occur in the target. These factors include: interactions of charged particles with matter; stopping power and ranges; energy straggling; and small angle multiple scattering. All of these phenomena effect the design of the target. In particular the chosen nuclear reaction, the target geometry and the amount of a radionuclide which may be produced are determined by these effects. To learn more about Nuclear Reactions and Target Physics follow the arrow. More Nuclear Reactions and Target Physics

10. Power deposited > 1 kwatt Beam Heating and Density Reduction The energy lost when charged particles pass through the target medium is dissipated in the form of heat. One of the most challenging problems in the design of cyclotron targets is finding methods to remove this heat from the target during irradiation. The heat generated in the target can often have several detrimental effects. A few of these are the target density reduction, chemical reactions occurring in the target material or products, and the potential damage to the target foil or body. To learn more about Beam Heating and Density Reduction, follow the arrow. More Beam Heating and Density Reduction

11. Target Foils More Target Foils • One of the most important components of any target system is the foil through which the beam enters the target material. This component is sometimes absent in solid targets, but is usually required in both liquid and gaseous targets. There are several important parameters in the choice of a foil. Often, the best choice with regard to one parameter will not be the best choice with regard to another parameter so compromises are often necessary. The important parameters in the choice of a foil are: • The thermal conductivity • The tensile strength • The chemical reactivity (inertness) • The energy degradation properties • Radioactive activation • Melting point • Each of these parameters interacts with the others in some subtle ways. For example, the stopping power will determine the amount of power deposited in the foil, which in combination with the thermal conductivity will set the temperature. The temperature will have an effect on the yield strength of the foil and may affect the chemical reactivity of the foil. To find out more about target foils, follow the arrow.

12. Power deposited > 1 kwatt Practical Target Design The practical design of a cyclotron target requires consideration of a large number of factors. Often optimizing one factor will result in the degradation of another factor. One example is the front foil. Making it thicker will increase the strength, but at the same time will reduce the energy of the beam on the target, increase the multiple scattering and require more cooling to be applied to the area. To see some examples of practical target design, follow the arrow. More Practical Target Design

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