⚛️ nuclear experiments

Optimization of 99mTc proton-induced production by means of cross-section measurements of technetium radioisotopes from molybdenum targets

This study optimizes the accelerator-based production of the medical radionuclide $^{99m}$ Tc by measuring proton-induced cross-sections on molybdenum targets, identifying 16 MeV protons and 0.5 mm enriched $^{100}$ Mo targets as ideal conditions to achieve a yield of 1.7 GBq/ $\mu$ A with radionuclidic purity compliant with European Pharmacopoeia standards.

Original authors: Dellepiane Gaia, D'Uva Sofia, Eggimann Lars, Gottstein Alexander, Juillerat Samuel, Kasanda Eva, Mateu Isidre, Scampoli Paola, Kadenko Ihor, Braccini Saverio

Published 2026-10-28

📖 4 min read🧠 Deep dive

CC BY 4.0

Original authors: Dellepiane Gaia, D'Uva Sofia, Eggimann Lars, Gottstein Alexander, Juillerat Samuel, Kasanda Eva, Mateu Isidre, Scampoli Paola, Kadenko Ihor, Braccini Saverio

Original paper licensed under CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

In the world of medical imaging, there is a single radioactive element that acts as a trusted guide for doctors. Called technetium-99m, this substance is the workhorse of nuclear medicine, used in millions of scans every year to help visualize the heart, bones, and organs inside the human body. Its value lies in a perfect balance: it emits a specific type of energy that cameras can easily detect, yet it disappears from the body quickly enough to keep radiation exposure low for the patient. For decades, this vital tool has been supplied by a fragile chain of events. Hospitals receive it from "generators," which are essentially radioactive batteries charged by a parent element called molybdenum-99. That parent element is created by splitting uranium atoms inside massive nuclear reactors. However, these reactors are aging, and frequent breakdowns have created a history of shortages, leaving hospitals without the scans they need. This vulnerability has driven scientists to look for a different way to make the medicine, one that does not rely on aging reactors or the splitting of heavy atoms.

The solution being explored involves using particle accelerators, specifically medical cyclotrons, which are machines already found in many hospitals to create other types of cancer treatments. Instead of splitting atoms, these machines can smash protons into a target made of a specific version of molybdenum to create the needed technetium directly. The challenge has been finding the exact settings to do this efficiently. If the energy is too low, nothing happens; if it is too high, it creates unwanted radioactive byproducts that could make the medicine unsafe for patients. A team of researchers from Switzerland and Ukraine set out to solve this puzzle by measuring exactly how different versions of molybdenum react when hit by protons of varying speeds. They did not rely on computer guesses or old data, which had often disagreed with one another. Instead, they built small, solid targets of molybdenum, some made of the natural mixture found in nature and others made of highly purified, enriched versions of specific isotopes. They fired beams of protons at these targets inside a specialized facility at the University of Bern, carefully controlling the speed of the particles and the duration of the exposure.

After the bombardment, the researchers measured the radiation coming from the targets with extreme precision. They tracked the creation of technetium and its various radioactive siblings, noting exactly how much of each was produced at different energy levels. This process was like tuning a radio to find the clearest signal while minimizing static; they needed to find the specific proton energy that produced the most of the useful technetium-99m while creating the least amount of the unwanted impurities. Their measurements revealed that previous data in scientific libraries often underestimated or overestimated how these reactions worked. By using a mathematical approach to separate the contributions of different starting materials, they mapped out the true behavior of the reactions up to an energy of 18 million electron volts. They found that the reaction works best when the proton beam is slowed down slightly before hitting the target, rather than hitting it at the machine's maximum speed.

The study identified a "sweet spot" for production. They determined that using a target made of highly enriched molybdenum-100, with a thickness of about half a millimeter, and bombarding it with protons at an energy of roughly 16 MeV, offers the best results. Under these conditions, a ten-hour run on a medical cyclotron could produce about 1.7 gigabecquerels of the useful technetium for every microampere of beam current. Crucially, this setup keeps the levels of radioactive impurities well below the strict safety limits set by European health authorities. The most significant impurity, a short-lived version of technetium, fades away quickly, while longer-lived contaminants remain at negligible levels. To prove their findings were not just theoretical, the team performed actual production runs using these optimized settings. The results matched their calculations almost perfectly, confirming that this method is reliable and feasible.

This work provides a clear, tested roadmap for hospitals to produce their own supply of this essential medical isotope. It demonstrates that with the right equipment and precise settings, the global supply of technetium-99m can be made more secure and independent of the aging nuclear reactor network. The researchers have shown that the path forward is not a distant dream but a practical reality, grounded in hard data and verified by real-world testing. By defining the exact energy and target thickness needed, they have removed the guesswork, allowing medical centers to plan for a future where this life-saving diagnostic tool is always available, regardless of the status of distant power plants.

Technical Summary: Optimization of 99mTc Proton-Induced Production via Cross-Section Measurements

Problem Statement
The global supply of Technetium-99m ( $^{99m}\text{Tc}$ ), the most widely used radionuclide for SPECT imaging, relies heavily on $^{99}\text{Mo}/^{99m}\text{Tc}$ generators produced via the fission of $^{235}\text{U}$ in aging nuclear reactors. This supply chain faces significant risks due to facility shutdowns and maintenance issues, necessitating alternative, accelerator-based production strategies. While the direct production of $^{99m}\text{Tc}$ from enriched $^{100}\text{Mo}$ targets using low-energy proton beams (<18 MeV) is a promising route, its optimization is hindered by significant discrepancies in existing literature regarding nuclear cross-sections. Accurate data on reaction cross-sections is essential to maximize production yield while ensuring radionuclidic purity meets clinical standards, such as those set by the European Pharmacopoeia.

Methodology
The study was conducted through a collaboration between the Laboratory for High Energy Physics (LHEP) at the University of Bern and the Taras Shevchenko National University of Kyiv. The research utilized the IBA Cyclone 18/18 cyclotron at the Bern University Hospital, providing proton beams up to 18.24(25) MeV.

Target Materials: Irradiations were performed on three types of molybdenum targets: natural Mo, 89.86% enriched $^{97}\text{Mo}$ , and 92.43% or 99.73% enriched $^{100}\text{Mo}$ . The isotopic compositions were verified via Inductively Coupled Plasma Mass Spectrometry (ICP-MS).
Irradiation and Measurement: Thin targets (solid foils or evaporated powders) were irradiated with controlled beam currents. Post-irradiation, activities were measured using an N-type High Purity Germanium (HPGe) detector.
Data Analysis:
- Cross-sections were calculated using standard activation equations, correcting for decay during irradiation and beam current fluctuations.
- For radionuclides produced via multiple reaction pathways (e.g., $^{93}\text{Tc}$ , $^{94}\text{Tc}$ ), a linear system inversion method was employed to disentangle individual reaction contributions based on measurements from targets with distinct isotopic compositions.
- Thick Target Yields (TTY) and radionuclidic purity were modeled using the measured cross-sections, mass stopping powers (calculated via SRIM-2013), and FLUKA simulations for energy degradation.
Validation: Two production tests were conducted using optimized parameters to validate the cross-section data and the theoretical yield predictions.

Key Contributions and Results
The paper presents a comprehensive set of experimental cross-section measurements for proton-induced reactions on molybdenum up to 18 MeV, covering the production of $^{93}\text{Tc}$ , $^{94}\text{Tc}$ , $^{95}\text{Tc}$ , $^{96}\text{Tc}$ , $^{97m}\text{Tc}$ , $^{99m}\text{Tc}$ , $^{101}\text{Tc}$ , and $^{99}\text{Mo}$ .

Cross-Section Data: The study provides new or refined cross-section data for several reaction channels, including $^{92}\text{Mo}(p,\gamma)$ , $^{94}\text{Mo}(p,2n)$ , and $^{100}\text{Mo}(p,2n)$ . The results generally show good agreement with available experimental literature but often diverge from TENDL nuclear data library predictions, which tend to underestimate or overestimate values depending on the specific reaction and energy range.
Optimization of Production Parameters:
- Energy: A proton energy of approximately 16 MeV was identified as optimal. While 18 MeV offers the highest theoretical yield, 16 MeV provides comparable yields for a 500 µm target while accommodating energy losses in beam transport and target windows.
- Target Thickness: A target thickness of approximately 0.5 mm (500 µm) was selected. While thicker targets (up to 900 µm) increase absolute yield, the 500 µm thickness offers a superior cost-efficiency ratio (yield per unit cost of enriched $^{100}\text{Mo}$ ) and better thermal management for high-current operation.
- Yield and Purity: For a 10-hour irradiation with a 16 MeV beam on a 500 µm enriched $^{100}\text{Mo}$ target, the calculated $^{99m}\text{Tc}$ yield is approximately 1.7 GBq/µA.
- Impurities: The study evaluated radionuclidic purity against European Pharmacopoeia limits. Key impurities include $^{94m}\text{Tc}$ , $^{95}\text{Tc}$ , and $^{101}\text{Tc}$ . The analysis shows that with a 10-hour irradiation and a cooling time of approximately 3 hours, the activity of $^{94m}\text{Tc}$ drops below the 0.02% limit. $^{95}\text{Tc}$ remains below its 0.07% limit for over 12 hours post-EOB. Long-lived impurities ( $^{95m}\text{Tc}$ , $^{97m}\text{Tc}$ ) are produced in negligible amounts.

Validation
Two production tests confirmed the feasibility of the proposed route:

A test at 10.4 MeV validated the cross-section measurements for various Tc isotopes.
A test at 16.1 MeV using a 99.73% enriched $^{100}\text{Mo}$ target yielded 271(14) MBq/µAh with a radionuclidic purity of 99.941(4)% (measured 2 hours post-EOB). These experimental results aligned closely with the theoretical predictions derived from the measured cross-sections.

Significance
The paper claims that its primary significance lies in providing high-quality, experimentally verified cross-section data that resolves inconsistencies in the existing literature. This data enables a rigorous optimization of the $^{99m}\text{Tc}$ production process, identifying a specific configuration (16 MeV protons, 500 µm enriched $^{100}\text{Mo}$ target, 10-hour irradiation) that maximizes yield while strictly adhering to clinical radionuclidic purity standards. The successful validation through production tests demonstrates the practical feasibility of producing high-purity $^{99m}\text{Tc}$ using medical cyclotrons, offering a viable alternative to reactor-based supply chains. The authors note that while the current tests were performed at low currents, the results provide a solid experimental basis for scaling production to clinically relevant beam currents.

Technical Summary: Optimization of 99mTc Proton-Induced Production via Cross-Section Measurements

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