This time, companies including Cardinal Health Inc. and Covidien PLC say advanced warning about a key coming plant outage helped them prepare. But the isotopes' very short lifespan means no one can stockpile supplies, and more than half the world's production capacity will be shuttered for about a month starting in mid-February.

Covidien told customers in a recent letter that it is using a "multifaceted" approach, but that "periods of significant shortages will still occur."

One of the top producers of material used to make isotopes, a reactor in Canada, has been sidelined since last May to fix a heavy-water leak, and the latest estimate is for a return by late March.

That is delayed from earlier estimates, which means the outage will overlap with a planned maintenance shutdown at the other major producer, in the Netherlands, which is slated to begin Feb. 19 and last six months.

The reactors produce material called molybdenum-99 that decays into technetium-99m, which is the world's most commonly used medical isotope.It is frequently used in scans to check for heart problems and cancer; there are an estimated 20 million nuclear medicine procedures in the U.S. each year.

The Canadian and Dutch plants are crucial global suppliers and particularly important for the U.S., where they are used to make nearly all isotopes. But both aging facilities have had issues and outages in recent years that have forced the industry to scramble for alternatives.

The supply chain is complex. In North America, MDS Inc.'s Nordion unit performs additional processing of material from the Canadian facility and then two companies—Covidien and privately held Lantheus Medical Imaging—make generators that produce the medical isotope.

These are distributed to hospitals and through radiopharmacies, where Cardinal has the biggest business.

Covidien, which gets most resources from the Dutch plant, is managing the looming shortfall by readying supplies of thallium, which is an older isotope used in heart scans; tapping molybdenum from other European reactors; and working with customers on efficiently using the isotopes they have.

The company announced plans last month to sell its radiopharmacy business to Triad Isotopes, Inc. for undisclosed terms in a deal expected to close in the second quarter.

By JON KAMP
Printed in The Wall Street Journal, page B4B

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“The federal government didn’t play the role it should have played there,” Dr. Robert Ouellet said Wednesday, after the association passed numerous motions prodding the government to dive back into the isotope business.

“There was a warning a year-and-a-half ago when the Chalk River reactor went wrong. They didn’t provide any views on what will come in the future. And this reactor is 53 years old.”

The government’s decisions on reactors have been made “for financial reasons,” Ouellet charges, and did not fully consider the effects on patient care.

The association demanded Wednesday that the federal government retain a leading role in providing medical isotopes for the world, and reconsider a decision to back away from isotope production.

Delegates at the CMA’s annual meeting in Saskatoon passed five motions they hope will help turn around a shortage of medical radioisotopes for diagnostic tests.

The anger and worry about the government’s handling of the nuclear reactor shutdown in Chalk River, Ont., and subsequently cancelled medical tests was palpable from doctors who spoke at the meeting.

“The federal government must be made accountable for this,” Ouellet told delegates.

“They lacked foresight, and of course right now there’s a shortage, and there will be additional costs for everyone.”

One passed motion expressed appreciation and admiration for the health-care workers across the country who have been trying to serve patients during the isotope shortage, declaring the CMA is “deeply troubled that the prolonged and unpredictable shortage of medical isotopes continues to compromise patient care.”

The CMA is also now demanding the government appoint an international expert panel to review the decision to abandon Chalk River’s Maple I and II research reactors, which were to have replaced the troubled National Research Universal (NRU) reactor. The NRU, which is currently shut down until at least early 2010 due to a heavy water leak, supplied one-third of the world’s isotopes for nuclear medical tests.

The isotope shortage has forced the cancellation of thousands of medical tests across the country.

Dr. Yolande Leduc told delegates she can’t understand why the government is backing away from isotope production.

“I’m also concerned Canada will be abandoning patients around the world,” the Quebec doctor said.

“I’m standing up to tell the federal government they don’t make sense.”

Doctors are also demanding the government conduct “open, meaningful and ongoing consultations with nuclear medicine physicians” and their associations on all federal decisions affecting the supply of medical isotopes.

They’re also calling for the government to create an emergency action plan for covering the increasing costs of isotopes during the shortage.

If provinces can’t track down medical isotopes, that’s one thing, Ouellet said. But if a province can’t get isotopes because it can’t afford the skyrocketing cost, “now the federal government is responsible for that and should pay.”

Physicians voted overwhelmingly in favour of calling on governments to ramp up the use of positron emission technology (a three-dimensional imaging technique that uses radiopharmaceuticals), and to “immediately invest heavily” in researching alternative production methods to the isotope technetium-99m, the isotope currently in short supply, and also in researching alternative isotopes that could be used in medical tests.

“This is a step to move us forward and to obtain the best care for our patients as possible,” the Canadian Association of Nuclear Medicine’s Dr. Christopher O’Brien said of the move to beef up PET technology.

By Janet French, Saskatoon StarPhoenix

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Each week, U.S. doctors prescribe some 300,000 medical-imaging tests that rely on technetium-99m, a radioactive isotope produced from molybdenum-99. About half of those tests measure heart function. Some map the spread of cancer. Others gauge the toxicity of cancer drugs on the circulatory system.

Neither the feedstock isotope nor the imaging isotope can be stockpiled because of their short radioactive half-lives (66 hours for molybdenum-99 and six hours for technetium-99m). New sources of molybdenum must be supplied to hospitals and imaging centers at least every two weeks.

“Right now, we’re managing [with the diminished supply], but just barely,” says Michael Graham, a nuclear medicine physician at the University of Iowa in Iowa City and president of the Society of Nuclear Medicine. “I’m concerned things are going to get worse by the end of this month.”

Indeed, “it’s predicted that in a week or 10 days, [U.S. supplies] could fall to perhaps 15 to 20 percent of our demand,” says Jeffrey Norenberg, director of radiopharmaceutical sciences at the University of New Mexico in Albuquerque and executive director of the National Association of Nuclear Pharmacies.

Five foreign reactors produce the vast majority of molybdenum-99. With an average age of 47 years — compared with an expected lifetime of only 35 years — those feedstock-producing reactors are all living on borrowed time. And they are subject to frequent outages for repairs.

The first reactor to go down this year was Canada’s 52-year-old National Research Universal reactor near Chalk River, in Ontario. On May 15, a small leak was identified in the reactor’s containment vessel.

That problem, initially expected to take perhaps a month to fix, is proving more difficult. An August 12 update by Atomic Energy of Canada Limited, which runs the facility, reports at least “nine sites likely requiring repair” and corrosion-fostered wall thinning and pitting of the reactor vessel. Currently, AECL now projects the reactor won’t return to service until at least the first quarter of 2010.

Almost two months to the day after AECL’s reactor went down, the 47-year-old Dutch High Flux Reactor in Petten began a month’s scheduled maintenance. That reactor should be back in service by the end of August. But delayed repairs of corrosion — which caused a temporary shutdown of the reactor last year — are slated to begin in February and last six months.

U.S. sources of molybdenum-99 have not existed since the mid-1980s. Concerned about the potential for catastrophic supply disruptions of this medical isotope, the Obama administration earlier this year “started plans to implement what we’re calling a long-term solution,” says Jean Cottam in the White House Office of Science & Technology Policy. “We decided it was time to move forward, as quickly as we could, to establish domestic production capabilities.”

Within two weeks, she says, her office at OSTP also could have a blueprint for domestic supply strategies to implement during periods of crisis, such as next spring. That could prove a “much worse situation [than now],” Cottam says, “because Petten will be down for much longer.”

By Janet Raloff
Science News
Web edition : Friday, August 14th, 2009

http://www.sciencenews.org/view/generic/id/46425/title/Isotope_crisis_threatens_medical_care____

Advanced Medical Isotope Corp. plans to test and develop prototype compact devices next week to produce isotopes including molybdenum-99 that are normally produced in a nuclear reactor, Jim Katzaroff, the company's chief executive officer, said Friday.

The Kennewick company was mentioned in a recent New York Times story on the shortage of medical isotopes because of the closure of two aging nuclear reactors in Canada and Holland that provide the bulk of the world's supply of medical isotopes.

Medical isotopes are radioactive substances used in tiny quantities for diagnostic imaging and treatment of various diseases including cancer.

Katzaroff said next week's test of the compact devices will be at Idaho State University in Pocatello, noting that computer simulations for the test have been going on for two years. It's a collaboration between Advanced Medical Isotope, the University of Missouri and a publicly traded company that he declined to identify.

Katzaroff said the Kennewick facility produces another type of diagnostic isotope.

Next week's tests involves shooting a beam into a light-enriched uranium solution, he said.

It'll show the economic feasibility of producing sufficient quantities of molybdenum-99, most commonly used to produce technetium-99m, which is used in about 80 percent to 85 percent of the world's diagnostic imaging procedures.

"If everything goes OK, we hope to be in production in three years," Katzaroff said.

Advanced Medical Isotope's production system is expected to be cheaper and quicker, compared with isotope production in a traditional reactor, he said.

Medical isotopes support about 20 million clinical procedures annually in the U.S., but more than 90 percent of the isotopes are imported.

According to projections by the National Academy of Sciences, the U.S. requires at least 5,000 curies of molybdenum-99 each week to meet current demand, which is expected to grow.

The U.S. isotope supply is vulnerable because the federal government doesn't have an advanced reactor energy policy and program, said Carl Holder, nuclear consultant and a member of Citizens for Medical Isotopes, a local nonprofit group working to promote the national production of medical isotopes.

Most U.S. research money on advanced reactors is spent abroad in France, Russia and China. It's drying up talent in America, Holder said.

"This crisis of medical isotopes has been on the horizon for years," said Carl Cadwell, a Kennewick businessman who has invested in Advanced Medical Isotopes. It's about helping improve people's health, said Cadwell, who also owns Cadwell Laboratories and the Tri-City Court Club.

The company can fulfill a critical need using the talent and existing research facilities in the Tri-Cities, Cadwell said.

By Pratik Joshi, Herald staff writer
www.tricityherald.com

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The 51-year-old reactor in Ontario, Canada, that produces most of this drug, a radioisotope, has been shut since May 14 because of safety problems, and it will stay shut through the end of the year, at least.

Some experts fear it will never reopen. The isotope, technetium-99m, is used in more than 40,000 medical procedures a day in the United States.

Loss of the Ontario reactor created a shortage over the last few weeks. But last Saturday a Dutch reactor that is the other major supplier also closed for a month.

The last of the material it produced is now reaching hospitals and doctors’ offices. The Dutch reactor, at Petten, is 47 years old, and even if it reopens on schedule, it will have to be shut for several months in 2010 for repairs, its operators say.

“This is a huge hit,” said Dr. Michael M. Graham, president of the Society of Nuclear Medicine and a professor of radiology at the University of Iowa.

There are substitute techniques and materials for some procedures that use the isotope, Dr. Graham and others said, but they are generally less effective, more dangerous or more expensive. With the loss of diagnostic capability, “some people will be operated on that don’t need to be, and vice versa,” he said.

Dr. Andrew J. Einstein, an assistant professor of clinical medicine at the Columbia University College of Physicians and Surgeons, said the isotope was used to determine if a patient had a coronary blockage that required an angioplasty or stent. Without the test, Dr. Einstein said, those invasive procedures would be performed on some who did not need them. His hospital is already sometimes using smaller doses of the radioactive drug than guidelines specify, he said.

In patients with a known cancer, the drug pinpoints additional tumors in bone. At a tumor site, new bone will develop, and new bone growth absorbs the radioactive material.

In breast cancer surgery, the radioisotope is injected to find the lymph node nearest the tumor, so it can be biopsied for signs of cancer, to determine whether more extensive surgery is needed.

The alternative is to inject a dye, which sometimes does not let the surgeon find the node.

Without the tool, Dr. Graham said, the quality of medical care is “dropping back into the 1960s.”

On Tuesday, Representative Edward J. Markey, a Massachusetts Democrat who is one of the House’s fiercest critics of the nuclear industry, declared that the United States was facing “a crisis in nuclear medicine.”

Mr. Markey, chairman of the House Energy and Commerce subcommittee on energy, called for establishing new production facilities in the United States. He joined the ranking Republican on the subcommittee, Representative Fred Upton of Michigan, to introduce a bill to authorize $163 million over five years to assure new production.

The White House is coordinating an interagency effort to find new sources of supply, involving the Nuclear Regulatory Commission, the Food and Drug Administration and the Energy Department, but officials said the process would take months.

The reactors are typically small — sometimes no larger than a homeowner’s trash barrel — but a complete setup costs tens of millions of dollars.

Tech-99m, as it is abbreviated, emits a gamma ray that makes its presence obvious. It has a half-life of six hours, meaning that it loses half its strength in that period. Thus it does its job quickly, without lingering to give the patient a big dose. But it also means the isotope must be produced and used faster than most other drugs.

Tech-99m is the product of another isotope, molybdenum-99, which also has a short half-life, 66 hours. Thus a week after it is made, less than a quarter of the molybdenum-99 remains. Stockpiling is not practical.

“You lose about 1 percent an hour,” said another expert, Kevin D. Crowley, director of the Nuclear and Radiation Studies Board at the National Research Council. “So time is of the essence.”

Molybdenum-99 is made when uranium-235 is split, but only about 6 percent of the fission fragments are molybdenum. Purification has to be done in a heavily shielded “hot cell.”

The common method is to put a uranium target into the stream of neutrons produced in the reactor as uranium is split. But the preferred material is a high-purity uranium-235, which is also bomb fuel.

Mr. Markey and others are trying to have the industry switch to low-enriched — nonweapons-grade — uranium.

Dr. Crowley said that could be done, although the industry has resisted.

The reactors’ poor condition has been obvious for a while. In 2007, Canadian safety regulators said the Ontario reactor should not restart, but the Canadian Parliament overruled them.

In 1996, the company that purifies the molybdenum from the Ontario reactor, MDS Nordion, contracted with Atomic Energy of Canada Ltd., which owns the reactor, to build two new ones. MDS Nordion paid more than $350 million for them.

But when the new reactors were started up, both showed a problem: as the power level increased, the reactors had a tendency to run faster and faster, a condition called positive coefficient of reactivity. That is a highly undesirable characteristic in a reactor, one that contributed heavily to the Chernobyl disaster in 1986. So Atomic Energy of Canada Ltd., which is owned by the Canadian government, said it would not open them.

For all the years that the Ontario plant was running or the replacements were under construction, other potential manufacturers believed they could not compete, said Dr. Dale E. Klein, a member of the United States Nuclear Regulatory Commission. And the business has always been small, he said, adding that a big pharmaceutical company “can make more on Viagra in two days than on tech-99m in a year.”

Several long-term alternatives are available. Babcock & Wilcox, a reactor manufacturer, has proposed a new kind of reactor that would manufacture molybdenum that could be siphoned off continuously.

In a few weeks, a company in Kennewick, Wash., Advanced Medical Isotopes, plans to test a new system, using a linear accelerator, a machine that shoots subatomic particles at high speeds.

Reactors in Belgium, France, South Africa and Argentina could also be used to make small amounts.

The High Flux Reactor at the Oak Ridge National Laboratory in Tennessee, owned by the federal government, and a research reactor at the University of Missouri, could do the work, but neither has the equipment in place to extract the molybdenum from the targets.

For the time being, said Dr. Crowley of the National Research Council, “we are in a triage situation.”

This article has been revised to reflect the following correction:

By MATTHEW L. WALD

The New York Times

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A version of this article appeared in print on July 24, 2009, on page A11 of the New York edition.

Correction: July 25, 2009
An article on Friday about the shortage of a radioactive drug crucial in testing for cardiac disease, cancer and kidney function in children omitted the given name and title of a man identified only as Dr. Klein, who said that potential manufacturers believed they could not compete with a reactor in Ontario. He is Dale E. Klein, a commissioner of the federal Nuclear Regulatory Commission.

The U.S. has long considered returning to domestic production of the molybdenum-99 isotope made at the Canadian reactor. The debate has tended to centre on the safety advantages of using low-enriched uranium, instead of the bomb-grade material used at Chalk River and the other four major reactors in Europe and South Africa.

An official from the National Nuclear Security Administration said this week the outage at Canada's National Research Universal reactor – which usually fills about 60 per cent of the U.S. demand for medical isotopes – has prompted a "supply crisis" that has captured the attention of officials in the White House.

"The United States is at the nexus of two related priorities: Discouraging the use of proliferation attractive (highly enriched uranium) in civilian commerce, and a health crisis from the lack of sufficient supplies of (molybdenum-99)," said a presentation Wednesday by Parrish Staples, director of the U.S. Office of European and African Threat Reduction. "The volatility of the current supply stream of (molybdenum-99) and the issue of (highly enriched uranium) in the civilian sector have drawn attention to the need for new producers to enter the (molybdenum-99) supply chain."

Staples said it would cost about $120 million (U.S.) to set up a process for domestic production of molybdenum-99 using low-enriched uranium.

National Nuclear Security Administration spokesperson Damien LaVera said the government is evaluating technologies that might ensure a secure, reliable supply of isotopes without using weapons-grade uranium. A Washington source confirmed the U.S. House of Representatives appropriations committee recently approved $12 million for the same long-term goals.

Alan Kuperman, director of the Nuclear Proliferation Prevention Program at the University of Texas in Austin, said the developments show the U.S. government is finally serious about domestic production.

"I think for Canada it's a signal that it would be a huge waste of money and effort to try and maintain isotope production in the long run," Kuperman said yesterday.

Natural Resources Canada spokesperson Micheline Joanisse said that while Ottawa supports the efforts by Atomic Energy of Canada Ltd. to renew its licence for the Chalk River reactor until 2016, it also welcomes any action to improve the stability of the global supply of medical isotopes.

Joanna Smith
Ottawa Bureau

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Mo-99 is the parent isotope of technetium-99m (Tc-99m), the most widely used medical radioisotope for molecular and nuclear diagnostic imaging procedures.

The North Billerica, Mass.-based Lantheus said the approval notification from the FDA and Health Canada were received within a one-week timeframe of Lantheus' filing of the sNDA and SNDS applications, respectively.

With these approvals, Lantheus said it will offer Tc-99m using Mo-99 derived from LEU targets. The LEU-derived Mo-99 has been tested and validated by Lantheus for use in its TechneLite generator line to ensure consistency and reliability, the firm said.

HealthImaging.com
Written by Editorial Staff   
Thursday, 09 July 2009

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In a July 7 letter to customers obtained by Reuters, the company's Nuclear Pharmacy Services unit in New York warned that on July 7-8 it would experience "the most significant shortage we have seen to date."

Cardinal Health spokesman Troy Kirkpatrick told Reuters the company has experienced sporadic shortages stemming from the May 17 shutdown of a nuclear reactor in Canada, but he said the company sees no financial impact from the shortage.

"Obviously, with the Canadian reactor down, it does impact the supply. But because of the arrangements we've made with our suppliers, we're looking at near-normal levels," he said.

Only five aging nuclear reactors produce molybdenum-99, the most commonly used medical isotope. Molybdenum-99 has a shelf life of just 67 hours, making it impossible to stockpile.

A medical isotope is a very small quantity of radioactive material used to perform nuclear medicine imaging tests. Isotopes are mixed with different solutions and injected into patients, where they give off energy that is read by special cameras.

Atomic Energy of Canada Ltd said on Wednesday it now expects its Chalk River nuclear reactor to be off line until late 2009, knocking out a key supplier of medical isotopes to North America. The United States has no domestic supply.

The shutdown has forced hospitals in the United States and Canada to ration supplies and delay medical tests.

Kirkpatrick said that aside from the shortages this week, the company expects supply problems on July 27, August 24 and 25 due to planned maintenance at two reactors in Europe.

Cardinal gets isotopes from two companies: privately held Lantheus Medical Imaging of North Billerica, Massachusetts, and Dublin-based Covidien Plc (COV.N: Quote, Profile, Research, Stock Buzz), another major U.S. supplier.

Lantheus got most of its isotopes from the Canadian reactor, but has cut a deal with other suppliers to cope with the impact of the shutdown.

Covidien gets most of its isotopes from a reactor in Petten, the Netherlands, but the company has said it can get isotopes from reactors in Belgium, France and South Africa.

Both companies process medical isotopes from reactors into lead-lined containers called generators.

Cardinal's network of nearly 160 nuclear pharmacies use the generators to process the isotopes into injectable form that can be read by special cameras to test for heart disease or to see if cancer has spread.

Kirkpatrick said the network allows the company to reach 70 percent of all U.S. hospitals within two hours.

The company offers several heart imaging agents including Myoview and Cardiolite, which rely on technetium, a decay product of molybdenum 99.

Cardinal told New York-based clients in the letter it hoped the supply situation would ease this week.

For July 7-8, it canceled all bulk orders of technetium, and limited bulk doses of Cardiolite and Myoview.

The company also said it was forced to limit the number of doses for each customer to about half of their usual order.

The Society of Nuclear Medicine said last month an e-mail survey of its 375 members -- which include doctors and nuclear medicine technicians -- found 91 percent had been affected by the shortage, with 60 percent postponing procedures and 31 percent canceling some.

MDS Inc (MDS.TO: Quote, Profile, Research, Stock Buzz), whose MDS Nordion division has an exclusive agreement to distribute Chalk River's medical isotopes to companies such as Lantheus, said the closure of the Dutch Petten reactor, planned for mid-July, will last about four weeks.

Cardinal's shares closed down 13 cents to $29.70 on Thursday on the New York Stock Exchange. (Reporting by Julie Steenhuysen; Editing by Phil Berlowitz)
 

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