Commercial accelerators dedicated to PET radioisotope production are limited both in energy (< 20 MeV) and in beam current (< 100 μA). Many production routes utilize gases or water as target materials, and therefore, external targets are preferred. Due to the relatively low beam current, extraction is not a problem. Internal targets are typically not implemented in PET cyclotrons because they need to be taken in and out of the cyclotron vacuum.
The choice of the right reaction and target material is crucial, as illustrated by the production of \(^{18}\text{F}\). Below are several nuclear reactions that can be applied for its production:
| Reaction | Description | Challenges |
|---|---|---|
| 20Ne(d, α)^{18}F | The nascent \(^{16}\text{F}\) will be highly reactive, diffusing and sticking to the target walls. | Difficult to extract due to reactivity. |
| 21Ne(p, α)^{18}F | Same as above, but the abundance of \(^{21}\text{Ne}\) is low (0.27%), requiring enrichment. | Low abundance of \(^{21}\text{Ne}\). |
| 19F(p, d)^{18}F | The product and target are the same element; poor specific radioactivity. | Poor specific radioactivity. |
| 16O(α, d)^{18}F | Cheap target, but accelerators capable of accelerating α particles to 35 MeV are rare and expensive. | Requires a rare and expensive accelerator. |
| 16O(d, γ)^{18}F | Small cross-section, no practical yields. | Small cross-section with no practical yields. |
| 18O(p, n)^{18}F | Expensive enriched target material but the proton energy is low (low cost accelerator). | Expensive enriched target. |
Not only the nuclear reaction but also the chemical composition of the target is important. For instance, irradiating \(^{18}\text{O}\) as a gas would be the purest target, but handling a highly enriched gas, along with hot-atom chemistry, is complicated. The best choice might be enriched \(^{18}\text{O}\) water as a target, as it is dominated by the \(^{18}\text{O}\) nucleus, and hydrogen does not contribute to unwanted radioactivity. Water containing \(^{18}\text{F}\) can be directly used in labeling chemistry or even injected into patients for applications such as PET bone scans with \(^{18}\text{F}\)-fluoride.
Some additional methods, such as the production of neon gas (\(^{20}\text{Ne}(d, α)^{18}F\)) and adding \(^{19}\text{F}_2\) gas as a carrier, yield \(^{18}\text{F}^{19}\text{F}\) which can be used for electrophilic substitution. However, this lowers the specific radioactivity of the labeled product.
A challenge in production is the heat generated when the beam is stopped in the target water. High-pressure targets that force the water to remain in the liquid phase help overcome some of these problems, but production is usually limited to beam currents < 40 μA. Gas and solid targets are more advantageous as they can withstand higher beam currents.
For the production of \(^{11}\text{C}\), the following reactions are commonly used:
The routine production routes of common positron emitters associated with PET are summarized in the table below:
| Radionuclide | Nuclear Reaction | Yield (GBq) |
|---|---|---|
| 15O | 14N(d, n)15O (gas target) | 15 |
| 13N | 16O(p, α)13N (liquid target) | 5 |
| 11C | 14N(p, α)11C (gas target) | 40 |
| 18F | 18O(p, n)18F (liquid target) | 100 |
Oxygen-15 is produced by deuteron bombardment of natural nitrogen through the 14N(d, n)15O nuclear reaction. Alternatively, the 15N(p, n)15O reaction can be used if a deuterium beam is not available, but this requires target enrichment. In nitrogen targets, 15O-labeled molecular oxygen is produced directly. Carbon-11 is produced by proton bombardment of natural nitrogen, and by adding oxygen to the target gas, 11CO2 is produced. Methane (11CH4) can be produced by adding hydrogen to the target gas.
Liquid targets are the most widely used for the production of 13N. The reaction of protons on natural water produces nitrate and nitrite ions, which can be reduced to ammonia. Alternatively, water targets can be directly converted into ammonia with the addition of a reducing agent like ethanol or hydrogen.