Mo99 and Tc99m in personalized medicine: easing the supply crisis

François Labarre, IBA Molecular.

8 Sept 2010

As the healthcare industry seeks to increasingly improve diagnoses, issues regarding efficiency, patient outcomes and cost continue to be top-of-mind.

 Personalized medicine, or “the use of new methods of molecular analysis to better manage a patient’s disease or predisposition to disease” [1], can provide patients with safer and more effective treatments; provide practitioners with access to innovative technologies; and reduce treatment costs for healthcare systems. So much so that PricewaterhouseCoopers anticipates the market for personalized medicine will grow to US$452 billion by 2015 [2].

One of the most significant components of personalized medicine is nuclear medicine, a discipline where small amounts of radioactive materials, known as radiopharmaceuticals, are used to diagnose or treat disease on a very individual basis. Particularly used in cardiology, oncology and neurology, nuclear medicine is able to measure the biological function of cells.

Current studies show that 40% of pharmaceutical treatments are inefficient, as they do not accurately target the underlying problem. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are non-invasive diagnostic imaging methods involving gamma rays that are used in nuclear medicine to visualize detailed, biological processes. By providing doctors with information about a body’s structure and function, diseases and their responses to treatment can be imaged and pinpointed at a very early stage, which can therefore lead to earlier, safer and more adequate treatments.

But currently impacting the efficiency of nuclear medicine is an ongoing shortage of the radioisotope Molybdenum 99 (Mo99). The production of this sensitive raw material is central in the production of Technetium 99m (Tc99m), which is used in nearly 60% of all patient scans conducted by nuclear medicine imaging specialists.

 Mo99, which has a half life of 60 hours, decays into TC99m, which has a half life of 6 hours. Due to its longer half life Mo99 is transported to medical facilities, where the TC99m is produced onsite as needed in technetium-99m generators. The need for Mo99 is estimated to be increasing at a rate of 3% each year.

 Most of the Mo99 is produced from highly enriched uranium from only five nuclear reactors around the world. The manufacturing and supply issues are the result of aging reactors around the globe which are experiencing repeated technical issues. For instance, two of the most important Mo99 suppliers, located in Canada and the Netherlands, have been shut down for repair due to their age. This has caused a recurrent shortage since 2009 with a severe occurrence this summer, and has been compounded by the fact that both reactors broke down at the same time. Other methods of producing Mo99 are possible but none so far are available to produce it in sufficient quantities.

These ongoing shortages severely affect the nuclear medicine industry — particularly imaging specialists — and as a result, their patients. Any halt in the production of Mo99 decreases the supply of products that specialists use in patient scans, resulting in fewer scans and a critical lack of diagnosis and treatment of potentially fatal diseases. Already there has been an estimated ten to 30% drop in patient scans since the first major shortage began on July 1.

Easing the Current Crisis

While the Mo99 shortage is clearly a major nuclear medicine hurdle, industry leaders such as IBA Molecular have implemented a number of measures to provide solutions and lessen the impact of the shortage for healthcare workers, and ultimately their patients.

During times of shortage, Mo99 is a scarce resource and its cost increases. IBA Molecular, for example, has focused on investing more to obtain additional supply needed to help alleviate the crisis for imaging specialists, even though this, in turn, has a direct impact on the price of the related solutions that these specialists use. The company secured a larger quantity of Mo99 by negotiating supplies from five reactors worldwide, and reorganized its production schedule to accommodate different delivery schedules of the raw material to provide equally for all customers, regardless of their size.

On September 1, IBA Molecular announced a partnership with the IRE (Institute for Radioelements) and the CEA (The French Alternative Energies and Atomic Energy Commission) to secure Tc99m supply beyond 2015 to meet the needs of approximately eight million tests per year in Europe.

Before the recent crisis began, IBA Molecular also reached out to nuclear medicine specialists to inform them that this crisis would take place. The company wanted to ensure that specialists understood the reasons behind the shortage and the expected rise in product costs, both of which are industry-wide issues. Early communication better enables specialists to prioritize and plan to adopt and implement new solutions at their disposal.

IBA Molecular’s extensive PET radiopharmaceutical network enables the company to provide widespread and accelerated solutions to the industry when it is affected by such manufacturing crises. Alternative products from its radiopharmaceuticals portfolio were put forward for use as substitutes for products affected by Mo99, including sodium fluoride, used for bone scintigraphy, and thallium chloride, a long-standing product in IBA’s portfolio, to conduct myocardial scintigraphy. These can both be used without relying on Tc99m.

While these are important options to ease the Mo99 crisis in the short-term, a long-term vision in nuclear medicine is imperative to be able to fulfill the substantial potential within personalized medicine. For example, despite efforts to upgrade existing nuclear reactors that are breaking down, new ones will need to be built in order to lessen the risk of future shortages and optimize production capabilities.

Over the long haul, the industry must adopt a number of changes, in particular related to the supply chain. While the industry expects that new reactors will be built, investments will need to be made by industry and government alike to secure the Mo99 supply chain. It is crucial to have cooperation from and with industry associations such as the European Association of Nuclear Medicine, the Association of Imaging Producers & Equipment Suppliers (AIPES), and governments throughout Europe to help make new projects and product solutions become a reality.

During this current crisis, and during any future ones, nuclear medicine producers must continue to focus on providing a pipeline of safe and reliable solutions to medical specialists in every corner of the globe, regardless of industry issues.

Looking ahead: developments in personalized medicine

Personalized medicine is an emerging discipline that will help overcome the substantial challenges healthcare systems face, by answering two main questions. Who is going to suffer from a disease? Is the treatment we deliver efficient, or will it be efficient? On one side is “diagnosis,” and on the other, “prognosis”. These questions address not only the health aspect of medicine, but the treatment costs involved as well, and a solid supply chain is imperative to ensure that these can be answered.

Looking forward, genetics, blood markers and imaging modalities such as CT and MRI will help to answer the diagnosis question, by screening a large scale of the population and predicting who will be affected by a disease.

But molecular imaging, by way of nuclear medicine, will be an extremely important tool to address the prognosis question. For instance, apoptosis tracers are currently being developed to help solve largely unmet medical needs in the area of cancer treatment, and reduce the overall cost of treating patients. These tracers could give a rapid view on the efficiency of a chemo- or radiotherapy in different types of cancer. By evaluating the efficiency of radiation treatment within days of treatment, instead of waiting for several months, chances will increase for the patient to receive the most appropriate therapy at the most appropriate time.

Additionally, new amyloid plaque tracers could allow for an accurate diagnosis and follow-up of Alzheimer’s disease, thus ensuring that the drug is being given to the right patients and is delivering the expected outcome.

Furthermore, nuclear medicine’s area of focus will eventually shift from disease diagnosis and evaluation of drug efficacy to encompass diagnosis, evaluation as well as therapy. Some therapeutics are currently being used in nuclear medicine, for example to alleviate pain from bone metastases. However they are not widely known, and represent only five percent of the nuclear medicine industry’s global activity.

As the nuclear medicine discipline continues to grow, and safe and reliable solutions consistently come to fruition, personalized medicine’s full potential will become clearer across all parts of the health ecosystem.

References

1. Personalized Medicine Coalition. www.personalizedmedicinecoalition.org
The PMC has produced a report: The case for personalised medicine. This details how personalized medicine plays an increasingly integral role in delivering high-quality, cost-effective health care and presents evidence that personalized medicine will continue to grow in importance as scientific breakthroughs are translated into a new generation of targeted therapeutics.

2. PricewaterhouseCoopers. The Science of Personalized Medicine: Translating the Promise into Practice. 8 December 2009.

François Labarre is senior vice president, Europe at IBA Molecular.

IBA Molecular is global developer, manufacturer and distributor of next generation radiopharmaceutical products and supporting services used in molecular imaging that respond to medical needs. The company’s radiopharmaceutical discovery-to-delivery development capabilities address major indications including oncology, cardiology and neurology, in PET, SPECT and therapy.

Please visit www.iba-molecular.com and www.iba-worldwide.com for more information about IBA Molecular and IBA group.