HFR

Until 2007 there was an almost uninterrupted supply of cheap subsidized reactor-produced isotopes, there was no need to search for alternatives. From January 2007 until February 2010  there has been at least six periods of serious disruption to supplies and since February 2010 after the shut-down of the HFR in Petten the world experiences the most serious period of medical isotopes shortages. Only in Canada the first disruptions were followed by serious debates on how to secure the domestic supply of radiopharmaceuticals in the nearby future and the future.

6.1 Discussion
The development of accelerator-based production of medical isotopes has always been thwarted in favor of the production with nuclear reactors. Policymakers are opting for research reactors, because they offer large scale production of medical isotopes. The continued disruptions, however, have proven that the reactor method is not safe and secure. And why should the isotopes production be dependent on a few worldwide monopolists? Cyclotrons offer the possibility to produce hospital-based medical isotopes.

Clinical and biomedical research communities in Canada have begun to look for alternative ways to produce technetium-99m needed for vital clinical procedures and also to explore the potential of alternative medical isotopes to replace technetium as the radiopharmaceutical label in clinical practice. Developments in this field can be observed in newspaper articles.
Let’s take for example a cardiac treatment center. Traditionally, technetium-99m covers about 80% of the isotopes supply used in this discipline. Due to the severe disruptions in the supply of technetium, cardiologists and other medical specialists are searching for the supply of cyclotron-produced isotopes that can be used as an alternative. These include cyclotron-produced technetium or PET isotopes that are performing better than technetium-based modalities. Cardiac PET includes a cyclotron where the lab makes its own medical isotopes. There is no longer any fear for shut downs in the supply of isotopes. PET rubidium-82, generated from cyclotron-produced strontium-82, is a major alternative to technetium. 18FDG-PET imaging tackles large arteries with atherosclerosis. The demand for cyclotron-produced thallium (heart) and iodine (thyroid) is increasing at the expense of reactor-based technetium used in cardiology.⁷⁷ The same trends can be observed in other medical disciplines among which cancer imaging and therapy. Also in the Netherlands medical centers have been started to look at other sources to secure their isotopes supply as a consequence of the ongoing crisis. More and more medical disciplines switch over to cyclotrons. Recently such decisions were made in Dutch hospitals in Alkmaar and Den Bosch.

Today Canada is frontrunner in the development of isotopes production by accelerators.
The Canadian subatomic physics laboratory TRIUMF  (TRI University Meson Facility) is involved in projects for accelerator-based production of technetium-isotopes and the production of gallium compounds for use as radiopharmaceuticals as alternatives to existing technetium-radiopharmaceuticals. The molybdenum-99 manufacturing method of TRIUMF involves the use of  a highly intense photon beam. Instead of thermal neutrons as in the reactor, electrons are used to irradiate the target material. Instead of high-enriched uranium targets as in reactors (vulnerable for nuclear proliferation), natural uranium is used as target material. In addition, the production of the positron emitter technetium-94 is proposed. This means that the produced technetium-isotopes can make use of the existing technetium-based radiopharmaceuticals for PET as well as SPECT imaging. The second project is the production of  gallium-68 (68Ga) and gallium-67 (67Ga) as alternatives to the 99mTc radiopharmaceuticals. A benefit of this alternative is that 67Ga will allow users the option of imaging using SPECT while 68Ga is a generator produced PET isotope that enables access to these agents in facilities without cyclotrons. This project is in co-operation with the Canadian partner MDS-Nordion, a leading global provider of medical isotopes and radiopharmaceuticals in molecular medicine.⁷⁸

Meanwhile, another Canadian company - Advanced Cyclotron Systems, Inc. (ACSI) - a world leader in the design and manufacturing of cyclotron equipment, submitted a proposal for a National Cyclotron Network to Produce Medical Isotopes that would fulfill all the Canadian 99mTc needs. ACSI’s TR24 cyclotron, the only 24 MeV cyclotron of its kind in the world, can produce PET and SPECT isotopes including 99mTc, 123I and 68Ge. ACSI is proposing the direct production of 99mTc on TR-24 cyclotrons as suggested by the Canadian Expert Review Panel on Medical Isotope Production. “A national network of eight strategically placed cyclotrons provides both a scalable and reliable source of isotopes and is financially self-supporting following a modest initial capital investment. Leveraging existing cyclotron technology and distribution centers, the network can begin operations within eighteen months (from January 2009) and would meet the entire Canadian medical isotope needs in two to three years.” According to their estimations the Canadian demand for 99mTc could be covered by cyclotron production between 2012 and 2014, much earlier as foreseen in the projected time schedule of the expert panel.⁷⁹

The preparations for the construction of the Pallas reactor are in full swing. Though officially there hasn’t been made a decision yet about the location (Zeeland or Noord-Holland), the board of the Dutch province Noord-Holland has invested €40 million in the construction of the Pallas. For a fraction of this amount Canadian researchers are working on solutions to tackle the urgent problems in the domestic supply of medical isotopes in the nearby future. It is highly likely that Canada will cover its domestic demand for technetium by accelerators in 2014. 

The prices of Canadian built medical cyclotrons are varying from €1,75 million to €4,20 million. Depending on the isotopes production, they can be delivered within a few months or a few year. The construction costs for the Pallas are estimated on €500 million. 

6.2 Conclusions
As described in Chapter 5 seven of the eight most popular reactor-based medical isotopes: molybdenum-99 (99Mo) (or direct production of 99mTc), iodine-131 (131I), phosphorus-32 (32P), , strontium-89 (89Sr), samarium-153 (153Sm), rhenium- 186 (186Re) and lutetium-177 (177Lu) can be easily made in substantial amounts with particle accelerators. The remaining popular reactor-based isotope chromium-51 (51Cr) is not an essential isotope. Similar cyclotron-produced isotopes performs better. Therefore, the widely used slogans of the nuclear industries indicating that reactor-based medical isotopes have been essential for nuclear medicine are false. The question “Is it possible to ban the use of a nuclear reactor for the production of radiopharmaceuticals?” can be answered with a straightforward ‘yes’.

This means that Pallas is not needed for the production of medical isotopes and leads one to suspect that other interests are involved. In the first place these are the commercial interests of Covidien - one of the subsidized monopolists on the global market of reactor-based medical isotopes, and in the second place Nuclear Research Group (NRG), which very much likes to play a major role in the area of nuclear consultancy and nuclear research. In addition it is important for the image of nuclear energy to maintain the coupling with the production of medical isotopes in the public debate and in the public perception.

A decision to develop radiopharmaceuticals with the use of reactors or cyclotrons is simply a choice and not a story of and reactors and accelerators. Cyclotrons are a logical choice. It saves costs and the environment. Moreover, cyclotrons guarantee a safe and secure supply of medical isotopes. Disruptions in the supply of isotopes will be over forever.

6.3 Recommendations
The Canadian researchers who invented the idea of a National Cyclotron Network to Produce Medical Isotopes show the route to a safe and secure production of radioisotopes. It can serve as a model for other nations. It also shows how quickly the transformation of a reactor-based to an accelerator-based production of medical isotopes can take place. If the Dutch government should choose now for such a transformation, like the Canadian government does, the cyclotron-based isotopes could easily cover the Dutch domestic demand for medical isotopes in 2016. Four cyclotrons in Groningen, Utrecht, Rotterdam and Eindhoven are enough to cover the Dutch domestic demand for technetium.

The use of PET/CT with PET isotopes in imaging and therapy presents a better alternative than gamma camera scintigraphy and SPECT with mainly reactor-produced isotopes. The share of reactor-produced medical isotopes will definitely shrink in the coming decades, while the share of PET isotopes is increasing steadily. Policy-makers can anticipate on this trend by making a choice for cyclotron-produced medical isotopes. Besides PET isotopes, this report has shown that all relevant reactor-based isotopes can be made by an accelerator. In addition, investing in cyclotrons also means investing in research for the development of new cyclotron-based pharmaceuticals, just like the current highly popular PET-pharmaceuticals.

77 Canwest News Service 11 July 2009: The new face of nuclear medicine: Radioactive dyes made at an Ottawa heart institute are saving patients from invasive procedures.
http://www.vancouversun.com/health/face+nuclear+medic ine/1781407/story.html
78 TRIUMF Submits Plans for Medical Isotope Alternatives. 17 Sep 2009 http://www.triumf.ca/headlines/current-events/triumf-submits-plans-for-m...
79 ACSI Announces New TR-24 Technetium Cyclotron, 10 January 2009http://www.advancedcyclotron.com/news/acsi-announces-new-tr-24-technetiu...

Source: The entire report "Medical radioisotope production without a nuclear reactor" (38 pages) is available at: www.laka.org/medical-isotopes.html Contact: Henk van der Keur, Laka Foundation, Ketelhuisplein 43, 1054 RD Amsterdam, The Netherlands.
Tel: +31 20 6168 294
Email: info@laka.org
Web: www.laka.org

Last year a commission of experts has advised the government of Canada, one of the major medical isotopes producing nations, to invest in accelerators for the production of among others radioisotopes, currently made by research reactors.71 Though the expert panel kept the option open to build a new research reactor, the Canadian government decided to cancel this option based on good arguments: “From a purely isotope perspective, outside the considerations of the other missions of a research reactor, the Government finds that the very high costs and very long lead times make this a less attractive option than others. Based on the experience of other countries, it would likely take a decade or more to bring a new research reactor on stream. Also, the significant fixed costs and production capacity would be disproportionate to Canada’s isotope needs and could not be recouped from the market. Waste liabilities associated with long-term reactor-based isotope production would be significant and again difficult to fully recover.” [..] “A research reactor is only one piece of the linear supply chain that exists today. Replacing one piece of a linear supply chain, such as simply replacing the NRU with another reactor, would do little to develop the diversity and redundancy that the Panel believed were critical for ensuring security of supply. The lesson learned is that more should be done to create cross-linked and distributed supply chains that are not as vulnerable to single-point failures. An announcement that a new research reactor would be built in Canada to produce medical isotopes would discourage investment in alternative sources of supply, both in Canada and in other countries. The supply chain would continue to remain vulnerable to the single-point-of-failure problem that exists today, and generators would likely be manufactured outside of Canada.”⁷²

Such a decision had to come to this in the end. The long history of choosing primarily research reactors for isotopes production has miserably failed. The continued disruptions in the supply of radiopharmaceuticals are the result of making wrong decisions. The development of the Maple-reactors in Canada is a perfect example to show the far-reaching consequences of such policy.

5.1 The MAPLE failure
In the mid 1990s the Canadian producer of radioisotopes MDS Nordion commissioned Atomic Energy of Canada Limited (AECL) to build two nuclear reactors. The two research reactors were named to the project name under which they were built: Multipurpose Applied Physics Lattice Experiment (MAPLE). Both reactors, Maple 1 and Maple 2, were especially designed for the production of molybdenum-99 (99Mo). Each of these reactors was to have the capacity to meet the world’s 99Mo needs, so that each would serve as a backup for  the other. With the prospect of the Maple reactors entering service in early 2000, the development of alternative production methods for 99Mo or 99mTc never reached maturity. And meanwhile, after more than ten lost years for the development of cyclotron-produced isotopes, AECL cancelled the Maple Project in May 2008. The Canadian Nuclear Safety Commission (CNSC) denied a license to operate the Maple reactors due to a design fault. In 1996, MDS Nordion agreed with AECL to pay US$140 million for the design, development and the construction of the two new reactors. In 2005, five years after the reactors had to be delivered, these costs were more than doubled (US$330 million) without the prospect that they will entering in service. Canadian radio-isotopes are therefore still produced with the aged National Research Universal (NRU) reactor of which the current license expires in October 2011.73 Meanwhile the construction the new research reactor in the Netherlands will start within a few months. The total costs are projected on €500 million and the reactor has to be operable from 2018.⁷⁴

5.2 Medical isotopes production is currently depending on five rickety reactors
Currently, around 95% of the worldwide medical reactor-produced isotopes are made with five aged research reactors in Belgium, Canada, France, The Netherlands and South-Africa which are frequently shut down for a longer period of time. The Canadian NRU reactor and the Dutch HFR together supply for about 80% in the worldwide demand of 99Mo, of which 60% is delivered by MDS Nordion (Canada) and the remaining part by Covidien Mallinckrodt
(The Netherlands). The other three reactors supply Europe and parts of Asia and also serve as back-ups when one of the large producers break down because of maintenance. All these reactors are 43 to 52 years old (mid 2010). The life span extension of the reactors cause - and will inevitably remain to cause –problems due to  age. The problems are not associated with the reactors themselves but with the infrastructure: leaking containment vessels and leaking pipes buried deep in shielding walls. Such problems are difficult to isolate and solve, resulting in prolonged shutdowns. The smaller reactors could increase their production capacity, such as the much named Maria research reactor in Poland (more than 35 years old), but none of these reactors has the capacity of the HFR or the NRU to take over the production rate of radioisotopes. The announcement of France to postpone  major repairs to the OSIRIS planned in 2010, because of the shutdowns of the NRU [May 2009 until August 2010(?)] and the HFR [February 2010 until August 2010(?)] will not bring any relieve in the continuing severe medical isotope shortages. Radioisotopes production with these wobbly nuclear reactors has been appeared very uncertain in the past years.75
Currently, around 95% of the worldwide medical reactor-produced isotopes are made with five aged research reactors in Belgium, Canada, France, The Netherlands and South-Africa which are frequently shut down for a longer period of time. The Canadian NRU reactor and the Dutch HFR together supply for about 80% in the worldwide demand of 99Mo, of which 60% is delivered by MDS Nordion (Canada) and the remaining part by Covidien Mallinckrodt
(The Netherlands). The other three reactors supply Europe and parts of Asia and also serve as back-ups when one of the large producers break down because of maintenance. All these reactors are 43 to 52 years old (mid 2010). The life span extension of the reactors cause - and will inevitably remain to cause –problems due to  age. The problems are not associated with the reactors themselves but with the infrastructure: leaking containment vessels and leaking pipes buried deep in shielding walls. Such problems are difficult to isolate and solve, resulting in prolonged shutdowns. The smaller reactors could increase their production capacity, such as the much named Maria research reactor in Poland (more than 35 years old), but none of these reactors has the capacity of the HFR or the NRU to take over the production rate of radioisotopes. The announcement of France to postpone  major repairs to the OSIRIS planned in 2010, because of the shutdowns of the NRU [May 2009 until August 2010(?)] and the HFR [February 2010 until August 2010(?)] will not bring any relieve in the continuing severe medical isotope shortages. Radioisotopes production with these wobbly nuclear reactors has been appeared very uncertain in the past years.⁷⁵

5.3 Can Pallas overcome the acute shortage of medical radioisotopes?
The current High Flux Reactor in Petten, The Netherlands, will be replaced by the Pallas. This new research reactor has to enter service in 2018. This means under the most favorable conditions, because there are normally years of delays in the construction of nuclear reactors. Considering the highly uncertain production of the NRU (permanently shut-down in 2011) and the HFR, Pallas offers no solution for a safe and secure supply of technetium-99m in the short term. Also the French Osiris reactor will shut down for a longer period by the end of 2010 or in 2011, the permanent shut-down is in 2015. Possibly Australian and German research reactors can take over a part of the production, however, as said before this will never be sufficient to keep up the supply of medical isotopes.

The recent decision of the Canadian government to cancel the construction of a new research reactor and to invest in the production of cyclotron-based radioisotopes have to be seen against this background. Hopefully this will be the first step in the revival of the original radioisotopes production methods: the charged particle accelerators. The development of a proton-induced neutron accelerator or the accelerator driven system (ADS), a sub-critical assembly driven by an accelerator, shows promising results. Such systems can be used until alternative medical isotopes produced by accelerators will arrive on the market. AMIC, a US company, in conjunction with researchers from a number of U.S. universities has tested ADS successfully for the production of molybdenum-99 and expects to start production in the nearby future to cover the US demand for technetium.⁷⁶ ADS is also a good alternative for the production of yttrium-90 (90Y), holmium-166 (166Ho), erbium-169 (169Er), and iodine-125 (125I), projected to be produced by Pallas.

71 Report of the Canadian Expert Review Panel on Medical Isotope Production, 30 November 2009. http://nrcan.gc.ca/eneene/sources/uranuc/pdf/panrep-rapexp-eng.pdf
http://nrcan.gc.ca/eneene/sources/uranuc/mediso-eng.php
72 Government of Canada Response to the Report of the Expert Review Panel on Medical Isotope Production. March 31, 2010
http://nrcan.gc.ca/eneene/sources/uranuc/pdf/isotopes-gc-re-eng.pdf
73 NTI - Canada, Updated May 2009 http://www.nti.org/db/heu/canada.html New Scientist 19 Jan 2010; Nuclear safety: When positive is negative http://www.newscientist.com/article/mg20527431.400-nuclear-safety-when-p...
74 Bouw Pallas kernreactor vertraagd http://www.rtvnh.nl/nieuws/index.asp?newsid=106000
75 Ruth, Thomas J.; The Medical Isotope Shortage: http://www.aps.org/units/fps/newsletters/200910/ruth.cfm
76 Globe Newswire, 3 Nov 2009: Advanced Medical Isotope Corporation Receives Positive Results from Initial Tests of a Proprietary and Innovative Method for the Domestic Production of Molybdenum-99 http://www.globenewswire.com/news.html?d=177328

The vast majority of the public thinks that research reactors, such as the High Flux Reactor (HFR) in Petten, the Netherlands, are essential for the supply of medical radioisotopes. And indeed these nuclear reactors are currently producing the vast majority of the isotopes. The nuclear industries like to maintain this widespread misunderstanding to justify their right to exist. A brief look in the history of nuclear medicine learns that all medical radioisotopes were originally manufactured by another type of production. The first medical applications of radioisotopes paralleled the development of the nuclear physics instruments which all these isotopes produced: the (charged) particle accelerators. Currently, these instruments are mistakenly purely seen as tools in fundamental scientific research.

2.1 Original production of radioisotopes
Tracer principal
Radiopharmaceuticals are used as radioactive tracers for the diagnosis and treatment of patients. The Hungarian chemist George Charles de Hevesy,  born as Hevesy György, published the first paper on the radioactive tracer concept in 1913. He coined the term radioindicator or radiotracer and introduced the tracer principle in biomedical sciences. An important characteristic of a tracer is that it can facilitate the study of components of a homeostatic system without disturbing their function. In 1924, the tracer concept paved the way for the use of radioisotopes as diagnostic tools. In 1927, the US physicians Hermann Blumgart and Soma Weiss injected solutions of bismuth-214 (214Bi) into the veins of men to study the velocity of blood.

Particle accelerator
After the discoveries of the cyclotron by Ernest Lawrence in 1931 and artificial radioactivity by Irène Curie and Jean-Frédéric Joliot in 1934, it was possible to make practically every imaginable radioisotope for use in diagnostics or in therapy. Isotopes such as iodine-131 (131I), phosphorus-32
(32P) and cobalt-60 (60Co) are already used in diagnostics and therapy since the mid-1930s.4 By bombarding an aluminum sheet with particles emitted by polonium Curie and Joliot created for the first time a radioactive element, which they baptized radio-phosphorus. Coupled with the Geiger counter’s detection capabilities, their discovery markedly expanded the range of possible radioisotopes for clinical tracer studies. Enrico Fermi produced a whole range of radioisotopes, including phosphorus-32 (32P). Soon 32P was employed for the first time to treat a patient with leukemia. Ernest Lawrence recognized the medical potential of radioisotopes. His brother, John, a hematologist, helped researched the field’s potential and established and administered the therapeutic procedures. In 1936 he treated a  28-year-old leukemia patient using 32P produced in one of his brother’s cyclotrons. It was for the first time that a radioisotope had been used in the treatment of a disease, marking the birth of nuclear medicine.

In 1938, Emilio Segre discovered technetium-99m (99mTc), and thyroid physiology was studied by using radioactive iodine. It was discovered that thyroid accumulated radioiodine (131I). Consequently it was soon realized that 131I could be used to study abnormal thyroid metabolism in patients with goiter and hyperthyroidism. More specifically, in patients with thyroid cancer, distant metastases were identified by scanning the whole body with the Geiger counter. The names radioisotope scanning and atomic medicine were introduced to describe the medical field’s use of radioisotopes for the purpose of diagnosis and therapy. Strontium-89 (89Sr), another compound that localizes in the bones is currently used to treat pain in patients whose cancer has spread to their bones, was first evaluated in 1939.5 All of these radioisotopes are now considered as ‘typical reactor-produced isotopes’
(The first successful cyclotron)

The first commercial medical cyclotron was installed in 1941 at Washington University, St. Louis, where radioactive isotopes of phosphorus, iron, arsenic and sulfur were produced. Soon there hadn’t been enough cyclotron capacity to fulfill the rising demand of isotopes. Civilian use of a military nuclear reactor provided relief to the producers of pharmaceuticals. The Manhattan Project – the US-led project to develop the first atomic bomb - resulted in an unprecedented expansion of radiation research and expertise, as well as its diagnostic and therapeutic application in nuclear medicine, including human experimentation. As a byproduct of nuclear reactor development, radioisotopes came to abound. As a result of this most radioisotopes of medical interest began to be produced in a nuclear reactor during World War II. Especially in the Oak Ridge reactor, which was constructed under the secrecy of the Manhattan Project. To protect this secrecy, the 32P produced by the reactor had to appear as if it had been produced by a cyclotron. Thus, 32P was sent from Oak Ridge to the cyclotron group at the University of California at Berkeley, from which it was distributed to the medical centers. The shortage of radioisotopes ended in 1945, when isotopes became widely available for research and medical use, including reactor-produced 131I from Oak Ridge. Globally, particle accelerators produced the vast majority of radioisotopes with medical applications until the 1950s when other countries followed the US by using reactor-based isotopes.

2.2 The rise of reactor-produced radioisotopes
After the war, the US continued its atomic research in a series of national laboratories, among them Los Alamos and Oak Ridge. These labs were supervised by the then Atomic Energy Commission (AEC), a governmental agency to coordinate the military, economic, political, and scientific work in atomic energy. The main mission of the AEC was promoting the military use of nuclear material, but “giving atomic energy a peaceful, civilian image” was also part of it. Including the promotion of research, among which radiobiology and nuclear medicine. Immediately after the war, radioisotopes flooded the laboratories and hospitals. In 1946, as part of the Isotope Distribution Program of the AEC, the Oak Ridge Reactor (see archive picture below) began delivering radioisotopes to hospitals and universities nationwide. In 1948 isotopes for biomedical research, cancer diagnostics and therapy even became free of charge, which can be considered as an early forerunner of the Atoms for Peace Campaign in the early 1950s aimed to promote the ‘the peaceful use of nuclear energy’. The rest of the western world followed this change in isotopes production. Entirely prospectless the particle accelerators tasted defeat in the competition with the subsidized nuclear reactors.⁶

The cyclotron-based radioisotopes production for medical applications revived a little in the 1950s, after the discovery that thallium-201 (201Tl) could be used as an ideal tracer for detecting myocardial perfusion. Thallous chloride labeled with 201Tl remains the gold standard for measuring cardiac blood flow despite the availability of technetium-99m myocardial perfusion agents.

(Oak Ridge National Laboratory – early 1950s)

2.3 Nuclear imaging modalities
Gamma camera
The era of nuclear medicine, as a diagnostic specialty began following the discovery of the gamma camera based on the principle of scintillation counting, first introduced by Hal Anger in 1958. Since then, nuclear medicine has dramatically changed our view of looking at disease by providing images of regional radiotracer distributions and biochemical functions. Over the last five decades, a number of radiopharmaceuticals have also been designed and developed to image the structure and function of many organs and tissues.

Molybdenum-99/Technetium-99m (99Mo/99mTc) generators
In 1959 the U.S. Brookhaven National Laboratory (BNL) started to develop a generator to produce technetium-99m from the reactor fissionable product molybdenum-99, which has a much longer half-life. The first 99mTc radiotracers were developed at the University of Chicago in 1964. Between 1963 and 1966, the interest in technetium grew as its numerous applications as a radiotracer and diagnostic tool began to be described in publications. By 1966, BNL was unable to cope with the demand for 99Mo/99mTc generators. BNL withdrew from production and distribution in favor of commercial generators. The first commercial generator was produced by Nuclear Consultants, Inc. of St. Louis, later taken over by Mallinckrodt (Covidien), and Union Carbide Nuclear Corporation, New York.⁷

Computed Tomography (CT)
CT is a medical imaging method employing tomography created by computer processing. The CT-scan was originally known as the EMI-scan as it was developed at a research branch of EMI, a company best known today for its music and recording business. It was later known as computed axial tomography (CAT or CT scan) and body section röntgenography. Although the term computed tomography could be used to describe positron emission tomography and single photon emission computed tomography, in practice it usually refers to the computation of tomography from X-ray images. The initial use of CT for applications in radiological diagnostics during the 1970s sparked a revolution in the field of medical engineering. In 1972, the first EMI-Scanner was used to scan a patient’s brain. CT provided diagnostic radiology with better insight into the pathogenesis of the body, thereby increasing the chances of recovery.⁸

Positron Emission Tomography (PET)
Another major breakthrough in the history of nuclear medicine arrived with the preparation of fluorodeoxyglucose (FDG) labeled with fluorine-18 (18F) in the mid-1970s. Use of 18F-FDG for studying the glucose metabolism lead to the development of the imaging modality positron emission tomography (PET). The use of 18F-FDG in combination with a PET-camera produced images of an excellent quality of the brains and the heart for studying aberrations, and the detection of metastases of tumors. Subsequently a large number of other 18F-labeled radiopharmaceuticals were developed and the use of new isotopes grows fast. PET scans are performed to detect cancer; determine whether a cancer has spread in the body; assess the effectiveness of a treatment plan, such as cancer therapy; determine if a cancer has returned after treatment; determine blood flow to the heart muscle; determine the effects of a heart attack, or myocardial infarction, on areas of the heart; identify areas of the heart muscle that would benefit from a procedure such as angioplasty or coronary artery bypass surgery (in combination with a myocardial perfusion scan); evaluate brain abnormalities, such as tumors, memory disorders and seizures and other central nervous system disorders; and to map normal human brain and heart function.⁹

Single Photon Emission Computed Tomography (SPECT)
At the end of the 1970s single photon emission tomography (SPECT) was introduced. Its development parallels the development of PET. SPECT images are produced from multiple 2D projections by rotating one or more gamma cameras around the body. Reconstruction using methods similar to those used in X-ray CT provides 3D data sets allowing the tracer biodistribution to be displayed in orthogonal planes. SPECT uses gamma-emitting radioisotopes, such as 99mTc and the cyclotron-produced indium-111 (111In) and iodine- 123 (123I). The advantages of SPECT over planar scintigraphy can be seen in the improvement of contrast between regions of different function, better spatial localisation, improved detection of abnormal function and, importantly, greatly improved quantification.¹⁰

Hybrids of CT, PET, SPECT and MRI
The last decade has seen the development of hybrid imaging technologies. PET or SPECT are combined with X-ray computed tomography (CT). Experts agree that PET/CT and SPECT/CT are superior techniques over stand-alone PET and SPECT in terms of diagnostic accuracy. Insiders expect that these hybrid imaging technologies will become the gold standard for conventional scintigraphy. Hybrid cameras combining PET and MRI have already been introduced. They also prospect the development of new hybrid forms for a certain organ or body part. These systems will offer the virtually unlimited potential of simultaneously acquiring morphologic, functional, and molecular information about the living human body.¹¹

2.4 Drawbacks of using PET,  SPECT and especially (devices combined with) CT
Despite the major improvements in nuclear medicine by using modalities such as CT, PET and SPECT, investigations in the US uncovered that 20 to 50% of these high-tech scans have been unnecessary, because they offer no support by making a diagnosis.¹² The U.S. National Cancer Institute reports alarming figures on the high radiation exposure of patients. It projects 29,000 excess cancers from the 72 million CT scans that Americans got in 2007 alone. Nearly 15,000 of those cancers could be fatal.¹³

An investigation by the US National Council for Radiation Protection and Measurements shows that frequent use of radioisotopes at one patient can result in a too high radiations exposure. It uncovered that the average dose has been increased from 3,6 millisievert (mSv) in the early 1980s to 6,2 mSv in 2006. The average dose per person is an average over the population of the United States.14 Apparently the enthusiasm to use these modern modalities has gone too far, which reminds to the widespread use of X-ray equipment in the 1950s.

By the end of February 2010, the U.S. Food and Drug Administration announced a federal program to prevent unnecessary radiation exposure from nuclear imaging devices and new safety requirements for manufacturers of CT scans. Medical doctors are urged to think twice before ordering such scans in order to weigh the risk and the benefit. According to estimates of David Brenner, director of Columbia University's Center for Radiological Research in New York,  20 million adults and one million children are being irradiated unnecessarily and up to 2%  of all cancers in the U.S. at present may be caused by radiation from CT scans.¹⁵ The American Society for Radiation Oncology (ASTRO) issued a six-point plan that has to improve safety and quality in using CT and other nuclear imaging modalities and reduce the chances of medical errors.¹⁶ So far, there are no figures known about the situation in Europe.

Though CT produces images with far greater clarity and detail than regular X-ray exams, it has been estimated that the average radiation dose of one CT scan is equal to roughly 500 chest X-rays. An international study, conducted by the IAEA and published in April 2010 has shown that some countries are over-exposing children to radiation when performing CT scans. These children are receiving adult-sized radiation doses, although experts have warned against the practice for over a decade. An additional problem in developing countries is that the available CT machines are older models without the automatic exposure controls found in modern equipment. This function can detect the thickness of the section of the patient´s body that is being scanned and can therefore optimize the level of radiation dose, avoiding unnecessary exposure. The IAEA has started a program to reduce unnecessary child radiation doses.¹⁷

Meanwhile newer CT technology has been developed to reduce a patient’s exposure to excess radiation. Patients who got a type of heart CT scan called coronary angiography received 91%  less radiation than those who were scanned with a traditional CT scanner. Although in the U.S. heart CTs only accounted for 2.3 million out of 65 to 70 million CT scans performed in 2006, they are worrisome because they deliver high radiation doses.¹⁸

2.5 Methods in radiotherapy
Brachytherapy is used for primary cancer treatment, for bone pain palliation, and for radiosynovectomy, used for patients that are suffering from joint pain. In cancer treatment the radionuclides are placed very close to or inside the tumor. During the therapy, controlled doses of high-energy radiation, usually X-rays, destroy cancer cells in the affected area. The radiation source is usually sealed in a small holder called an implant. Implants may be in the form of thin wires, plastic tubes called catheters, ribbons, capsules, or seeds. The implant is put directly into the body. Brachytherapy dates back to the time before the discovery of the cyclotron when natural radioisotopes, such as radium-226 (226Ra), were used in the treatment. Currently, common radionuclides are iridium-192 (192Ir), yttrium-90 (90Y), iodine-125 (125I) and palladium-103 (103Pd).¹⁹

(accelerator used in fundamental scientific research)

4. From Radioisotopes to Medical Imaging, History of Nuclear Medicine Written at Berkeley, 9 September 1996. http://www.lbl.gov/Science-Articles/Archive/nuclear-med-history.html Lawrence And His Laboratory - A Historian's View of the Lawrence Years: Ch2 The Headmaster and His School. Lawrence Berkeley National Laboratory, 1981. http://www.lbl.gov/Science-Articles/Research-Review/Magazine/1981/81fchp...

5. Chemistry Explained - Nuclear Medicine: http://www.chemistryexplained.com/Ne-Nu/Nuclear-Medicine.html

6. Rheinberger, Hans-Jörg; Putting Isotopes To Work: Liquid Scintillation Counters, 1950-1970.  Max-Planck-Institut für Wissenschaftsgeschichte, Berlin 1999. pp.4-5 http://edoc.mpg.de/get.epl?fid=3199&did=46724&ver=0

7 The Technetium-99m Generator: http://www.bnl.gov/bnlweb/history/tc-99m.asp

8 Bartlett, Christopher A.; EMI and the CT Scanner [A] and B] www.blackwellpublishing.com/grant/docs/10EMI.pdf

9 Positron Emission Tomography – Computed Tomography (PET/CT); Radiology Info http://www.radiologyinfo.org/en/info.cfm?PG=pet

10 What is SPECT?: http://www.spect.net/: Nuclear Technology Review 2007, IAEA. p.61

11 Nuclear Medicine 2020: What Will the Landscape Look Like? http://www.molecularimaging.net/index.php?option=com_ articles&view=article&id=17661:nuclear-medicine-2020-what-will-the-landscape-look-like

12 Where Can $700 Billion In Waste Be Cut Annually From The U.S. Healthcare System? Robert Kelley, Thomson Reuters, October 2009. http://www.ncrponline.org/PDFs/Thomson_Reuters_White _Paper_on_Healthcare_Waste.pdf

13 Radiation From CT Scans May Raise Cancer Risk, 15 December 2009 http://www.npr.org/templates/story/story.php?storyId=121 436092&ft=1&f=1007

14 Medical Radiation Exposure of the U.S. Population Greatly Increased Since the Early 1980s, NCRP Press Release, 3 March 2009. http://www.ncrponline.org/Press_Rel/Rept_160_Press_Rel ease.pdf
People Exposed to More Radiation from Medical Exams, Health Physics Society, 9 March 2009. http://hps.org/media/documents/NCRP_Report-People_Exposed_to_More_Radiat... ms_9Mar.pdf

15 Radiation Risks Prompt Push to Curb CT Scans. Wall Street Journal, 2 March 2010. http://online.wsj.com/article/SB100014240527487042998 04575095502744095926.html

16 Medical Group Urges New Rules on Radiation. New York Times, February 4, 2010. http://www.nytimes.com/2010/02/05/health/05radiation- .html

17 IAEA Aims to Reduce Unnecessary Child Radiation Doses - New Study Shows Global Variation in Dose Levels for Child CT Scans. IAEA, 23 April 2010: http://www.iaea.org/NewsCenter/News/2010/childcts cans.html

18 Newer heart CTs deliver far less radiation. Reuters, 24 February 2010

19 Flynn A et al. (2005). “Isotopes and delivery systems for brachytherapy”. in Hoskin P, Coyle C. Radiotherapy in practice: brachytherapy. New York: Oxford University Press.

(November 13, 1998) Russian Prime Minister Primakov has authorized the start of negotiations between Russia and Euratom about the supply of up to 600 kg of High-Enriched Uranium (HEU) for the 45-MW (th) High Flux Reactor (HFR) in the Netherlands.

(502.4956) Laka Foundation - The export of HEU from Russia to Euratom would set a precedent, because Russia has agreed only to the export of HEU under bilateral agreements. In 1996 with France and with Germany this year. But no Russian HEU has left Russia yet since neither the French nor the Russians has agreed on transport arrangements. Russia doesn't have a bilateral agreement for nuclear trade cooperation with Euratom. A new Russian-Euratom agreement would permit the export of up to 600 kg of HEU for the HFR at Petten, the largest producer of radioisotopes in Europe. The 600 kg would be enough for 15 years, the time the HFR is foreseen to be in operation. The HFR was started up in 1962 and is operated by the European Union as part of its Joint Research Center (JRC). The day-to-day operation and maintenance is done under contract by the Dutch Energy Research Foundation (ECN).

The US sees the HFR as a key target in their Reduced Enrichment in Research and Test Reactor (RERTR) program. They have been trying to convince the EU to convert the reactor from HEU with 93% U-235 to fuel-enriched 20% U-235. Until recently JRC and Petten officials had resisted the conversion as being too long and too costly and as a potential risk for the reactor's performance. The new HFR director, Joel Guidez, said the reactor needs about 40 kg HEU per year. The HFR might need an additional 120 kg of HEU because it could take two or three years to get a license if the decision is made to convert and a gradual conversion could take some more years. Fuel supply for the HFR is assured until the end of the present program (December 1999). A gradual conversion would cut costs of conversion dramatically, because both reactor downtime and HEU expenditures would be reduced. This strategy was successfully conducted by Guidez at the French Osiris reactor. Early next year consultants from AEA-Technology will have completed a technical- economic study of the conversion study, which would serve as a decision basis for JRC and HFR. The new high-density silicide fuel needs to be made by the French firm Cerca beginning next year.
The spent fuel pool of HFR is expected to be full at the end of this year. At present, about 800 fuel elements are stored in the HFR pool.
If the AEA study concludes that conversion is not worthwhile, Petten has a contract with the organization responsible for storage of radioactive waste COVRA, to take the HFR spent fuel for interim dry storage in its facility near the Borssele reactor. But the facility for high-level waste has still to be built, so there would be a big storage problem. If the HFR is to be converted, the spent fuel could be sent back to the US.

If the decision to convert is made, then the US Department of Energy (DOE) would take back all the fuel. DOE officials are set to visit Petten in November and are expected to talk with Guidez at the 21st international meeting on RERTR in Sao Paola, Brazil this October. The DOE seems to agree with the supply of Russian HEU to the HFR on condition the HFR would be converted.

Sources:

• Nuclear Fuel, 5 October 1998
• 1997 Annual Report HFR, Joint Research Center

Contact: Laka Foundation
Ketelhuisplein 43
1054 RD Amsterdam
The Netherlands.
Tel: +33-20-6168 294; Fax: +33-20-6892 179
E-mail: laka@antenna.nl
 

Waste storage too expensive for producers

Dutch nuclear utilities (ECN, EPZ, SEP) like to sell their shares in the central organization for nuclear waste (COVRA) to the state because they would step out of nuclear power soon. But the most important reason for them is likely: less expenditures for storage of their nuclear waste.
Those three now own 90% of the COVRA shares, but only paid ƒl 2.4 million (US$1.3 million) of the costs each. The Dutch ministry of environment (VROM) has the remaining 10% of the shares, but has invested up to now the lion's share of the much-higher-than- expected costs and losses: ƒl 60 million. COVRA claims the costs are higher than expected due to delays in construction of the building to store high-active nuclear waste (HABOG). The delay is caused by the fact that the highest court, the Raad van State, this summer destroyed the license for the HABOG. This year the COVRA is to lose ƒl 5 million on a turnover of ƒl 10 million. ECN operates the Euratom High Flux Reactor (HFR) in Petten, EPZ is owner of the Borssele nuclear reactor, and SEP is the owner of the closed Dodewaard reactor. Inside the HABOG, high-active reprocessing wastes returning from France and UK are to be stored and (possibly) spent fuel from the HFR (see related article). Borssele is to be closed by the end of 2003, and the HFR by about 2015.
Sources:

• Volkskrant (NL), 6 October
• NRC (NL), 8 October 1998