In recent times, the tech sphere has been abuzz with news related to "new isotopes." In early February, the Institute of Modern Physics, Chinese Academy of Sciences (hereinafter referred to as IMP-CAS), and its collaborators announced the first synthesis of the new isotope Actinium-203 in the scientific journal Chinese Physics Letters B; two weeks later, they announced the synthesis of new isotopes Ruthenium-160 and Tungsten-156 in the scientific journal Physical Review Letters; at the end of March, they announced the China Advanced Facility for Exotic Isotope Beams (CAFE2) breaking the beam intensity record...
When it comes to "isotopes," many immediately think of cancer-targeting drugs. Targeted therapy, utilizing isotopes as the primary material, is considered a "ray of hope" in cancer treatment due to its minimal side effects compared to radiation and chemotherapy, and its precise efficacy. These drugs, administered through intravenous injection, can accurately locate tumor sites and target cancer cells.
It's understood that currently, due to factors such as core technology, equipment, and innovation, 90% of medical isotopes used in China rely on imports, with the most advanced among them—alpha isotope targeted drugs—entirely dependent on imports.
So, behind these positive developments with new isotopes, what is China's capability for large-scale isotope production? Is there a possibility of a turnaround in the development of targeted drugs? Reporters from China Science News delved into the source of the new isotope news—the Institute of Modern Physics, Chinese Academy of Sciences—to find out.
Alpha Medical Isotopes: "A Scarce Resource Worldwide"
In the research park of the Institute of Modern Physics, Chinese Academy of Sciences, in Lanzhou New Area, a medical isotope research platform based on a high-current superconducting linear accelerator (IP-SAFE) is under rapid construction.
Covering an area of over 140 acres, with a total construction area of 28,200 square meters, once completed, it will become the world's first high-output, high-purity therapeutic alpha isotope production platform.
"The accelerator radiation technology is a new trend and direction for preparing medical isotopes. Through this platform, we hope to achieve key core technologies and equipment for mass production of medical isotopes independently controllable, solve the 'neck-breaking' problem faced by medical isotope raw material supply, and promote the high-quality development of China's precision radiotherapy industry and supply chain," said Hu Zhengguo, Secretary of the Party Committee and Deputy Director of the Institute of Modern Physics, Chinese Academy of Sciences.
Medical isotope targeted drugs, including diagnostic single-photon isotope drugs and positron isotope drugs, as well as therapeutic alpha isotope drugs and beta isotope drugs. Among therapeutic isotope drugs, compared to beta isotope drugs, alpha isotope drugs can more precisely, effectively, and safely treat tiny scattered metastatic tumors. They complement external beam irradiation for solid tumors and are currently a technological high ground in the development of medical isotopes and a hot spot for international radiotherapy and new development trends.
Li Guohong, Director of the Technology Transfer and Industrialization Department of the Institute of Modern Physics, Chinese Academy of Sciences, explained that due to the high purity and difficulty of chemical separation required for therapeutic alpha isotopes, the difficulty of large-scale production is significant. These drugs are scarce worldwide and come with a high price tag. Consequently, the technology for large-scale production of alpha isotopes has become a research hotspot in developed countries, with its core technology strictly controlled.
"In the development of large-scale production of alpha isotope targeted drugs, China is just getting started," Li Guohong said. Faced with the grim challenge of the dramatic increase in cancer patients and deaths from cancer in China, as well as the growing urgent demand for medical isotopes and the cruel reality that most medical isotopes, especially alpha medical isotopes, need to be imported, the construction of a large-scale production platform for medical isotopes, especially alpha medical isotopes, has become a top priority.
Key Core Technologies Conquered
In June 2021, the National Nuclear Agency, together with the Ministry of Science and Technology, the Ministry of Public Security, the Ministry of Ecology and Environment, the Ministry of Transport, the National Health Commission, the National Medical Insurance Administration, and the National Medical Products Administration, officially issued the "Medium and Long-Term Development Plan for Medical Isotopes (2021-2035)," becoming China's first landmark document focusing on the application of nuclear technology in medical and health fields. The plan proposes that by 2025, a batch of key core technologies for the development of medical isotopes will be achieved.
"There are over 280 naturally occurring isotopes in nature, and more than 3,300 artificial ones have been synthesized so far. Researching the decay properties of these isotopes not only has significant scientific implications but also helps apply them in various aspects of people's lives," said Zhang Zhiyuan, a researcher at the Institute of Modern Physics, Chinese Academy of Sciences, to China Science News.
Since the 1990s, researchers at the institute have been engaged in isotope research and development, successively producing isotopes such as Mercury-208, Cobalt Cyanide, Cadmium-109, Thulium-167, and Germanium-68. Today, they have also produced a variety of medical alpha isotopes such as Radium-223, Actinium-225, Molybdenum-99, and Technetium-99m, meeting medical purity standards and achieving breakthroughs in high-purity, high-efficiency isotope production and automated isotope separation technology.
Zhang Zhiyuan explained that relying on the Heavy Ion Accelerator at the Institute of Modern Physics, Chinese Academy of Sciences, supported by the strategic scientific and technological project "Future Advanced Nuclear Fission Energy—ADS Transmutation System," researchers have solved scientific problems related to the production and separation of alpha isotopes, and conquered some key core technologies.
He said that in terms of accelerator production for alpha medical isotopes, the Institute of Modern Physics, Chinese Academy of Sciences, has also mastered and broken through the key technologies of continuous-wave ion superconducting linear accelerators through the development of the China Advanced Facility for Exotic Isotope Beams. They have constructed the world's first 20 Megavolt/10 Milliampere continuous-wave proton superconducting linear accelerator, achieving continuous-wave proton beams of hundreds of kilowatts running continuously for hundreds of hours for the first time internationally, and stable acceleration of continuous-wave 10 milliampere proton beams, creating conditions for the mass production of alpha medical isotopes.
"Creating alpha isotopes" and "becoming a targeted therapy" are still steps apart.
"At present, the Chinese superheavy element research accelerator, mainly used for scientific research, can only prepare a small number of alpha isotope samples," said Hu Zhengguo. "We hope to produce a clinical trial batch this year."
He explained that the medical isotope R&D platform currently under construction is essentially a scaled-up version of the Chinese superheavy element research accelerator. It uses a similar superconducting linear accelerator scheme and, once completed, will have a beam intensity and power five to ten times greater than similar foreign facilities, with production also expected to be five to ten times higher.
"As a national research institution, we focus on major national needs and strive to apply our fundamental research to the development of key technologies. In doing so, we not only serve public health but also transform our research achievements into new productive forces," Hu Zhengguo noted.
Internationally, in 2014, Bayer acquired Norwegian company Algeta for $2.9 billion, gaining access to its radium-223 chloride therapy, Xofigo, which after its 2017 market release, earned €408 million in annual sales. In 2017, Novartis acquired French radiopharmaceutical company AAAP for $3.9 billion, whose main product, the radiopharmaceutical 177Lu-DOTATATE, is used for treating advanced neuroendocrine tumors and was approved by the FDA in 2018, generating $650 million in sales that year. On December 26, 2023, BMS (Bristol Myers Squibb) acquired RayzeBio (focusing on Ac-225 isotope therapies) for $4.1 billion.
"From isotopes to new drugs, this process requires a collaborative system involving multiple industries and fields; it's not something a few research units can achieve alone," Hu said. The Institute of Modern Physics at the Chinese Academy of Sciences is collaborating with institutions like the Fujian Institute of Physical Structure, Ningbo Institute of Materials Technology and Engineering, and Shanghai Institute of Materia Medica, along with various hospitals, to spearhead the development of alpha isotope targeted drugs.
"We hope more research institutions and companies will join us in this endeavor," Hu Zhengguo added.
