Adoption of Cyclotron as an Alternative Source for Radioisotope Boosting Nuclear Medicine Market

Nuclear medicine is a highly multi-disciplined medical imaging speciality sector that uses small amounts of radioactive material in order to diagnose and treat diseases related to gastrointestinal system, neurology, endocrine system, cardiology and cancer. Nuclear medicine technique provides enhanced early detection, accurate diagnosis, rapid results, detailed description of various diseases and helps in adopting additional treatment plans when compared to traditional imaging methods.. The adoptions of nuclear medicine for effective usage in integrated structure-function imaging, has made it a preferred imaging technique over traditional methods and increase its use in diagnostic radiology and various therapeutic indications. Radiopharmaceuticals containing a radioactive tracer are generally inhaled, swallowed or injected into the patient and the gamma-rays emitted by this material are used by the SPECT and PET imaging modalities to display images. Advancements in radioactive tracers are providing practical methods for studying the limited metabolic activities of bones and teeth, hence has found a role in dental research, development of next-generation therapeutic radiopharmaceuticals conjugated with antibodies and peptides is expanding new areas of research. Approximately 40-42 million nuclear medicine procedures (diagnostics & therapeutics) are performed annually, of which 16-17 million procedures are performed in U.S. alone.

According to IQ4I Analysis,’’ Nuclear Medicine/Radiopharmaceutical’’ global market is expected to reach $9,367.8 million by 2024 growing at a mid single digit CAGR. Increasing radioisotopes application, rise in public awareness, use of SPECT/CT and PET/CT imaging scans (hybrid imaging) and advancements in technology are driving nuclear medicine market growth. In addition, increasing need in emerging markets, production of radiopharmaceuticals from cyclotrons, efficient diagnosis and treatments, emerging radioisotopes and replacement of old/traditional equipments are the opportunities likely to propel the growth of nuclear medicine market.

There is increase in aging population, change in lifestyles, urbanization and rise in obesity have lead to increase in number of people suffering from conditions related to oncology, cardiology, neurology, nephrology, thyroid and others which is driving huge demand for production of SPECT and PET radioisotopes, but closure of reactors have lead to shortage in production of radioisotopes, hence in order to meet the shortage the hospitals, diagnostic centers, academic and research institutes are shifting their radioisotope source from nuclear reactors to cyclotrons. Cyclotrons are used in large hospitals to locally produce short-lived tracers used in PET imaging. Some of the advantage of using cyclotron for producing is high uptime, decentralized production allows back up chains, small investment compared to nuclear reactor and little long-lived radioactive waste. The worldwide installed base of cyclotrons exceeds 550 units as of 2017 with approximately 40 to 50 new units added per annum. Some of the radiopharmaceuticals produced from cyclotrons are Ga-67, In-111, I-123, Tl-201 and F-18 of which F-18 is mostly used isotope. The F-18 is used in diagnosis of inflammatory disease, prostate cancer, cardiac perfusion, neurology and bone scan.

The radioisotope suppliers have increased the installing cyclotrons for production of radioisotopes. For instance, the medical production facility in Australia by ANSTO, the twin PETNET cyclotrons at Lucas Heights are small cyclotrons dedicated to making Fluorine-18 for FDG synthesis. Lantheus is boosting production of thallium-201 in its cyclotrons and is currently operating at full capacity to meet the demand for this alternate cardiac imaging agent. The RDS cyclotron, manufactured by Siemens is one of the most frequently used in PET around the world. Some of the other cyclotron in Australia are operated commercially in Melbourne by Cyclotek while others are based at the Royal Prince Alfred Hospital (NSW), Peter MacCallum Cancer Institute (VIC), Austin Health and Medical Imaging Australia (VIC), Royal Brisbane Hospital (QLD), Wesley Hospital (QLD) and Sir Charles Gairdner Hospital (WA).

Recently in June 2018, IBA a world’s leading provider of solutions for the diagnosis and treatment of cancer signed a formal contract with the Arizona Isotopes Science Research Corp. (AZI) to install a Cyclone 70 system in Arizona, USA. The installation of the system is worth between $16 and $20 million to IBA and the project is fully financed.

Asian market is withdrawing its dependency on nuclear reactors and adopting hospital-based cyclotrons for radioisotopes production is also adding to its market size growth. China, India, Brazil and South Africa have reactors and other production unit to increase isotopes production. The half-life of radiopharmaceuticals varies for each radioisotope. FDG has a half-life time of only 2 hours and Tc-99 has 6 hours which restricts their usage only to hospitals where cyclotron production facility is integrated. If the cyclotron production facility is far from the diagnostic centers or hospitals the radionuclide has to be transported, administered to the patients and imaging has to be done within the half-life period of the isotope. In the reactor dependent supply chain, a lot of radioisotope is lost due to their radioactive decay which also adds to the cost.

Although the cost of setting up the cyclotron in a hospital is very high, when compared to the cost required to set up a nuclear facility the investment is small. The cyclotron production facility not only includes equipment cost but also includes the cost of building, packaging, quality check and technicians recruited that build up to the investment cost. In the coming years, the bargaining power of buyers might increase because of the introduction and large-scale adaptation of cyclotrons decreasing the dependence on large reactors for raw material production. In addition to this there is also increased price competition among companies who are producing radiopharmaceuticals from cyclotrons.

Rhenium from generator comes with a carrier using up metallic rhenium as targets but cyclotrons produce rhenium with tungsten targets. Even though rhenium from generators is advantageous with respect to price and quantity than their cyclotron counterparts, only few generators are available worldwide for rhenium production. Cyclotron produced rhenium is more preferred for diagnosis as they are carrier free and has a purity of around 99.6%. Rhenium is 77th most abundant metal.

In U.S. the radioisotopes used are mainly imported from other countries especially Canada and the lion’s share of the radioisotopes imported are used for medical purposes. Canada is one of the largest producers of Tc-99m in this region because of the presence of NRU (National Research Universal) reactor as it has a 40% share in the worldwide production, the planned closure of the NRU reactor in Canada by 2018 poses a great threat for the nuclear medicine market in this region. However the country has started to make their own isotopes in order to meet the shortage of isotopes through obtaining approval for cyclotrons for production of isotopes. For instance, in 2018 Northstar Medical Technologies received approval for routine production of active Mo-99, aiming to meet 110 six-day TBq per week, half of US demand and in addition the company in September 2015 collaborated with Westinghouse Electric Company to investigate Mo-99 production in nuclear power reactors using its Incore Instrumentation System.

In 2017, Telix Pharmaceuticals Limited entered into manufacturing partnership with JFE Engineering Corporation an engineering and manufacturing company with extensive expertise in the installation of cyclotron infrastructure and radiopharmaceutical manufacturing in Japan. IBA Cyclone 18 MeV Cyclotron for preparing beam activation and Zr-89 (Zirconium) production was installed by JFE at Yokohama (Kanagawa) facility in early 2018 which will represent the first commercial production in Japan.

Some of the cyclotrons operated in Australia are Cyclotek in Melbourne, Royal Prince Alfred Hospital (NSW), Peter MacCallum Cancer Institute (VIC), Austin Health and Medical Imaging Australia (VIC), Royal Brisbane Hospital (QLD), Wesley Hospital (QLD) and Sir Charles Gairdner Hospital (WA). Some of the medical cyclotrons in China are Cyclone-18 by IBA present at Xi’an Chang and Hospital which produces F-18, N-13 and C-11. Compared with North America and Western Europe, the demand for medical cyclotrons in China in health care is in rapid growth.

The major players operating in Nuclear medicine market Curium Pharma (France), Bayer AG (Germany), GE Company (U.S.), Cardinal Health (U.S.), Jubilant Life science (India), Lantheus Medical Imaging (U.S.), Novartis International AG (Advanced accelerator) (Switzerland), South African Nuclear Energy Corporation (NTP Radioisotopes SOC Ltd) (South Africa), Siemens AG (Germany) and Fujifilm Holding Corporation (Japan).

Some of the other emerging companies operating in Nuclear medicine global market include Perma-Fix Environmental Services, Inc. (Perma Fix Medical SA) (Poland), Board of Radiation & Isotope Technology (India), Institute of Isotopes (Hungary), Isotopia Molecular Imaging Ltd. (Israel), Orano Med (Areva Med) (U.S.), Curium Pharma (France), Eckert & Ziegler Strahlen (Germany), IsoAid LLC (U.S.), Shine Medical Technologies, Inc (U.S.), Theragenics Corporation (U.S.), Isoray Medical Inc (U.S.) and other companies.

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