Latest Technologies in Nuclear Medicine

Nuclear medicine is not a new field, but it is a vital one, as with the help of radiopharmaceuticals and imaging systems for their accumulation and distribution (combined PET-CT and PET-MRI technologies), doctors have accurate tools for diagnosis and treatment in cardiology, oncology, neurology, and other fields of medicine.

However, it is important to distinguish between the concepts of nuclear medicine, radiology, roentgenology, and radiation therapy. Nuclear medicine uses isotopes for diagnosis and treatment, which are injected into the body as radiopharmaceuticals. Radiology includes MRI, ultrasound, and X-rays, as these studies use electromagnetic wave radiation. Radiology is a branch of diagnostics that uses X-rays only. Radiation therapy, on the other hand, uses both X-rays, only more powerful than in diagnostics, and high-power gamma radiation (4-25 MeV generated by a linear accelerator, 1.25 MeV from the Co-60 isotope), and proton and neutron therapy. Brachytherapy is also a type of radiation therapy.

According to the Euratom Supply Agency Annual Report for 2022, medical facilities worldwide, including more than 10,000 hospitals, use radioisotopes in nearly 100 different nuclear medical procedures. This results in nearly 49 million medical procedures worldwide each year. In the European Union alone, more than 1,500 nuclear medicine centers provide care to approximately 10 million patients each year. The market for new radiopharmaceuticals is expected to grow significantly in the coming years, as the use of medical radioisotopes in cancer treatment is rapidly expanding.

Innovative technologies in medicine correspond to each stage of the industrial revolution. During the first industrial revolution, the transition from manual to mechanized production occurred, and in medicine, René Laennec invented the stethoscope in 1816. The second industrial revolution was marked by the invention of electricity, the commercial light bulb, the telegraph, and the advanced factory production line. In medicine, it was marked by the invention of the electrocardiogram by August Waller in 1887, who projected the heartbeat recorded by the Lippmann capillary electrometer onto a photographic plate, allowing for real-time recording of the heartbeat.

The driving force behind the third industrial revolution, known as the digital revolution, was the spread and widespread use of computing, particularly personal computers. In the medical field, in the 1960s, David Kuhl and Roy Edwards developed cross-sectional computed tomography and implemented it in the SPECT scanner, which was later taken as a basis by Godfrey Hounsfield and Alan Cormack in 1972. The fourth industrial revolution, which is happening now, is characterized by substantial amounts of data, hyperconnectivity, and neural networks, which has led to the creation of self-driven cars and the development of artificial intelligence, in particular in nuclear medicine.

Artificial Intelligence in Nuclear Medicine

Last year, in 2023, the first Conference “Artificial Intelligence and Informatics in Nuclear Medicine” was held to discuss current achievements, challenges, and the future of artificial intelligence and informatics in nuclear medicine. According to the information presented during the Conference, nuclear medicine is several steps behind radiology in the development of commercially available algorithms. Although the prospects of artificial intelligence (AI) and neural network-based technologies in nuclear medicine for image processing and pattern recognition were recognized in the early 1990s, it took more than 20 years to implement this technology in nuclear medicine.

AI, machine learning, and distance learning tools can be used to improve software and hardware, which will help to reduce the duration of imaging, reduce the amount of dose administered, and obtain more accurate spatial and temporal resolution, resulting in clearer images.

The use of AI will also change the way images are read and interpreted in nuclear medicine. Tedious and time-consuming tasks, such as highlighting the necessary structures, will soon be fully automated thanks to AI algorithms. Images will be displayed with predefined suspicious areas, which will significantly accelerate their visual analysis by nuclear medicine specialists and radiologists. In addition, AI will be able to detect diseases, make predictions, and classify them based on molecular features of images with a low error rate. However, before AI can be widely used, it is necessary to demonstrate its reliability and clinical or economic value for patients.

AI is also necessary to assist in the process of data integration. Automated complex data analysis is needed to process substantial amounts of complex data of diverse types and identify patterns that will then become the basis for biological hypotheses.

The U.S. Food and Drug Administration (FDA) released in 2021 its first Action Plan for AI and Machine Learning in Medical Device Software, which outlines a holistic approach based on full product lifecycle oversight to further develop the enormous potential these technologies have to improve patient care while ensuring safe and effective software functionality that improves the quality of medical devices.

The Action Plan outlines five measures that the FDA intends to implement, including:

1. Update the regulatory framework by developing draft guidance on a predefined change management plan (for machine learning software);
2. Support the development of good machine learning practices for evaluating and improving machine learning algorithms;
3. Promote a patient-centered approach, including ensuring transparency of device performance for users;
4. Develop methods for evaluating and improving machine learning algorithms;
5. Promote pilot projects to monitor effectiveness in actual conditions.

Thus, artificial intelligence is currently used in hardware and software to automate some imaging parameters (e.g., patient positioning and scan time); create high-quality quantitative images (e.g., using AI to correct scatter, attenuation, and motion, reconstruct images, or eliminate noise); analyze and interpret images.

Robots will Change the Production of Radioactive Isotopes

In the United States, research and production of medical isotopes are carried out at national laboratories and university accelerators. Scientists create the desired radioisotopes through nuclear transmutation by irradiating targets consisting of enriched stable isotopes. However, after irradiating the targets, scientists need to chemically separate a small amount of the produced radioisotopes from the bulk of the target material and impurities.

Radiochemical separation can be performed in two ways:

• desktop manual processing with gloves on, which threatens to expose the researchers involved in the process and limits the output capacity of production batches;
• processing in well-protected special hot cells, but they still use mechanical manipulators from the 1940s, which require significant maintenance, are expensive, and have limited mechanical capabilities.

In order to upgrade and improve the production of medical isotopes, scientists at the U.S. Department of Energy’s Argonne National Laboratory have launched a project to create a telecommunications robotic system that will introduce a new type of radioisotope processing station. To this end, scientists are developing a two-armed robot that will perform operations in hot cells. The system will use a virtual reality system that will allow scientists to see the interior of the boxes. In addition, accurate real-time visualization of remote radiochemical treatment in a hot cell requires a sophisticated 3D workflow integrated with the robotic system.

The developed technology will allow to safely work with samples that are 10 times more radioactive without using hot cells and will increase the ability to produce the necessary isotopes.

Improving the Methods of Delivery of Radiopharmaceuticals

According to the SE “USIE IZOTOP”, almost all radiopharmaceuticals (except for a limited part of diagnostic ones) and 100% of the relevant equipment are supplied from abroad, but the full-scale invasion of Ukraine by russia led to the closure of airspace, which complicated the supply routes and increased the waiting time for patients to receive medicines and diagnostic products.

To simplify the supply routes for radiopharmaceuticals and accelerate their delivery to hospitals and patients, in addition to traditional methods of air transportation, cars, etc., the world uses pipe and drone delivery.

The method of delivering radioisotopes through pipes is not new, but pipes are usually used on a smaller scale, for example, in hospitals or postal systems for example.

In Canada, this method, the so-called “rabbit line”, has been used since the early 1980s. This is a 2.5 km long pneumatic pipe that runs between the TRIUMF Particle Accelerator Center in Canada and the University of British Columbia Hospital and delivers isotopes (carbon-11, fluorine-18, and nitrogen-13) from the Center to the hospital for use in medical imaging, particularly PET scanning. The pipe is located 1.5 km underground, with 0.5 m of radiation-protective concrete above it.

The technology uses compressed air to deliver isotopes from the Center to the hospital. When a package leaves TRIUMF, an air valve is left open for about a minute to force it through the pipe. With an average speed of 60 km/h, the capsule covers the distance in about 2.5 minutes, slows down at the end, and arrives upright at the receiving station located under the hospital.

It is important to note that the technology adheres to strict Nuclear Safety Commission restrictions that clearly define which isotopes and in what quantities can be delivered in this way.

The most important advantage of this technology is the delivery speed, and it is also safer and there is a low probability of an accident or radiation exposure or contamination.

The delivery of radioisotopes by drones can be a promising area in nuclear medicine, especially in situations where the speed of delivery and access to drugs are critical. Although, of course, the use of drones to deliver radiopharmaceuticals has both advantages and challenges that may arise in the process.

Among the advantages of using drones is fast delivery to hospitals, especially in remote, hard-to-reach areas where access for people may be limited. Also, compared to the method of delivery by road, drones can fly around obstacles and change routes depending on the conditions, which allows them to deliver radiopharmaceuticals even in unforeseen situations. In addition, the use of drones can reduce transportation costs and minimize traffic on roads.

However, when using drones, companies may face challenges such as ensuring safety during the delivery of radioisotopes by drones and the potential impact on human health and the environment, as radioactive materials can be dangerous if misused or in the event of accidents; technical limitations of drones, such as payload capacity and flight range, which will reduce efficiency for delivering large volumes of radioisotopes over long distances.

Canada was the first country to test the use of drones to deliver radioisotopes. Thus, in 2023, Drone Delivery Canada received permission from Transport Canada to fly beyond line-of-sight and transport dangerous goods, including medical radioisotopes, using drones. This became possible thanks to the implementation of the Care by Air project, a 13.4 km commercial route for the transportation of medical radioisotopes using drones. The first test flight within the project using the Sparrow drone took place in October 2022. Before this, the company’s procedures, practices, and personnel were inspected by the Canadian Nuclear Safety Commission and Transport Canada to ensure compliance with the strict safety requirements necessary for both flying beyond the visual line of sight and transporting medical radioisotopes.

Following Canada, the UK has started testing the technology of delivering radiopharmaceuticals by drones. In 2024, the Institute of Physics and Engineering in Medicine funded the Pioneering project, which involves the use of drones to deliver radiopharmaceuticals between hospitals in the West Midlands. Currently, more than 59 radiopharmaceutical pharmacies provide services to nuclear medicine facilities in the UK, which can use drones to supply departments within an 80 km range. Drones can also increase access to targets such as gallium-68 that are currently limited by road, thereby expanding nuclear medicine capabilities nationwide. The transportation of radiopharmaceuticals by drone has not been conducted in the UK before, and the Civil Aviation Authority has not yet gone through the relevant certification process.

Therefore, while the delivery of radioisotopes by drones has significant potential, it is important to carefully consider all the benefits and challenges to ensure safety, efficiency, and regulatory compliance.

In Conclusion

Nuclear medicine has an immense potential for diagnosing and treating patients. However, according to the European Industrial Association for Nuclear Medicine and Molecular Health (Nuclear Medicine Europe), nuclear medicine faces challenges that are important for further development and are related to the safe and reliable supply of existing and future radioisotopes, regulation of the industry, support for innovation and technical development; raising awareness and understanding of the benefits of nuclear medicine among healthcare professionals, patients, and the public.

However, these are not the only challenges that nuclear medicine professionals have to overcome. In particular, the EU currently needs to pay more attention to overcoming dependence on russia in the supply chain of medical radioisotopes.

First, some EU research reactors producing vital medical radioisotopes depend on russian fuel and materials. High-abundant low-enriched uranium (HALEU) is currently not produced in the EU but is imported from the United States and russia. However, U.S. reserves are estimated to last until 2035-2040, depending on the actual consumption of existing stocks. Currently, some EU research reactor operators that have already obtained licenses for alternative fuel have gradually ceased fuel supplies from russia. Some are actively participating in Euratom’s research projects to develop alternative fuels and break the russian monopoly on fuel supply for research reactors.

Second, the EU is also dependent on russia for enrichment of stable isotopes needed to produce several important medical radioisotopes, including ytterbium-176, which is needed to produce lutetium-177. The enriched isotopes will also be needed in the long term to develop alternative ways to produce technetium-99m, molybdenum-98, and molybdenum-100.

Nevertheless, the European Commission continues to support the safe, high-quality, and reliable use of radiation and nuclear technologies in the healthcare sector. In 2022, the foundation was laid for the implementation of the SAMIRA action plan in three priority areas:

• ensuring the supply of medical radioisotopes.
• improving radiation protection and safety in medicine.
• promoting innovations and technological development of ionizing radiation use in medicine.

Uatom.org editorial board