Technetium-99m Availability: Production and Industry UpdatePosted on: 12.19.19
Overall this year, there has been some unsteadiness in the supply chain for Moly-99 (Mo-99), which in turn affects the supply of technetium-99m (Tc-99m). For operators of gamma cameras, availability of the radiopharmaceutical gives cause for concern.
David Pellicciarini, Vice President, Pharmacy Safety, Practice & Technical Operations for Cardinal Health, spoke to us about the current situation with Tc-99m and what is expected in the future.
Origins and nature of Tc-99m
To understand why the supply chain is so sensitive, it helps to understand the Tc-99m production process. It is produced as a decay product of Mo-99. Mo-99 does not exist in nature but is most-often created using a nuclear reactor. It is developed by either fissioning uranium targets or bombarding non-radioactive molybdenum targets with neutrons.
The isotopes of Mo-99 and technetium-99m have short half-lives – 66 hours for Mo-99 and just 6 hours for Tc-99m. This means they must be produced continuously and cannot be stockpiled. As a result, whatever is happening at the reactor can impact the Mo-99 and technetium-99m supply. Anything that might prevent the production of Mo-99 can very quickly impact the supply chain.
There have been intermittent interruptions over the last several months, and our team, in partnership with Cardinal Health, works together to minimize any customer impact. “During a shortage, we have staff working overtime and delivery drivers running irregular routes to maximize the reach of the supply we have,” says David Pellicciarini.
The supply chain
The majority of suppliers of Mo-99 are located outside of the United States. Just one Mo-99 manufacturer has recently been approved in the U.S., and they are expanding their operations.
After the Mo-99 is produced at the reactor, it is sent to Tc-99m generator manufacturers. From there, the Tc-99m generators are shipped to radiopharmacies, where the generators are used to prepare the Tc-99m-based radiopharmaceuticals for patient use.
The short, six-hour half-life means that radiopharmacies such as Cardinal Health need to continually be preparing radiopharmaceuticals to deliver to customers. When there is a disruption upstream in the supply chain, such as a reactor issue or a delay in the production of generators, the radiopharmacies may be challenged to fill all customer orders.
Domestic Production of Mo-99
The supply chain is complex, but we do anticipate that there will be more U.S.-based Mo-99 suppliers in the future. In addition to the one current US-based Mo-99 supplier, there are several other companies who are working on getting approval to supply Mo-99. We’re encouraged to see multiple companies taking the initiative and making the investment to improve the domestic supply.
You might wonder why we don’t already have reliable domestic production of Mo-99. In the past, we relied heavily on supply from Canada as they are so close to us geographically. However, Canada stopped producing Mo-99 for the global market, which meant other suppliers had to step up production. It also meant our other suppliers were much further away.
“I think because Canada did such a great job and were so reliable for decades, domestic production wasn’t seen as an urgent issue in the U.S.,” says Pellicciarini. “Supply issues aren’t nearly as bad as they were a decade ago, but they still happen. We work hard to mitigate any impact to our customers and patients, and most of the time, we’re able to do that.”
Needless to say, we look forward to the availability of more domestic Mo-99 suppliers, but it does take a fair amount of time for them to get set up. They have many facets to organize, including manufacturing operations, licensing and regulatory requirements, transport, and even specialized containers needed to carry the product. Ultimately, they also need FDA approval. This creates a two-to five-year window from now for new suppliers to be up and running.
The American Medical Isotopes Production Act
The premise of the American Medical Isotopes Production Act is: “To promote the production of molybdenum-99 in the United States for medical isotope production, and to condition and phase out the export of highly enriched uranium for the production of medical isotopes.”
Under the Act, the Secretaries for Energy and Health and Human Services have to make an assessment on whether there are adequate supplies of Mo-99 coming into the U.S. from sources other than highly enriched uranium (HEU) sources.
There is a date of January 2, 2020 for the secretaries making a recommendation on this. No more licenses are meant to be issued for the export of highly enriched uranium to produce Mo-99 unless there is an inability of the U.S. market to be supplied by low enriched uranium (LEU) sources.
New producers are using non-HEU methods, and the majority of current suppliers have already converted to non-HEU production of Mo-99.
David Pellicciarini notes that Cardinal Health participates in several industry associations and groups, including the Organization for Economic Co-operation and Development (OECD) to help influence policy and communicate critical messages about the needs of the U.S. market.
They hope to see less of the Mo-99 supply issues that have impacted customers and patients in the past and are hopeful for a more stable supply in the near future.
Inside the ASNC SPECT Imaging GuidelinesPosted on: 10.18.19
The field of nuclear cardiology has expanded greatly over the last few years, prompting an update of the ASNC SPECT Myocardial Perfusion Guidelines.
Updated guidelines were published in May 2018 and include newer generation cameras, processing techniques, and key topics such as radiation reduction. These guidelines have also been endorsed by SNMMI. A core tenet of the guidelines is giving clinicians a review of the available imaging tools in nuclear myocardial perfusion imaging and focusing attention on choosing the right test for the right patient at the right time.
We caught up with Karthik Ananthasubramaniam, MD, one of the section lead authors of the guidelines to discuss their process and what the new guidelines mean for physicians. He is part of a team lead by Dr. Sharmila Dorbala that includes clinicians, physicists, and individuals who use SPECT on a daily basis.
Dr. Ananthasubramanium says that, while the essential principles of the original 2010 guidelines remain intact, this update was about providing a detailed update on the modern equipment and techniques that physicians and technologists use today. SPECT remains the dominant modality for stress testing, with over 8.5 million studies performed annually.
With physicians all across the world using SPECT as a frontline testing option, it’s essential that it is done the right way. Here are some of the key updates in the new guidelines:
The guidelines are easier to read
As Dr. Ananthasubramaniam describes, one of the key goals of the committee was to make the guidelines more visually appealing to read. This is one way that they can be made more accessible and useful to those who need them.
While the 2010 version had some visual aids, this new 2018 update contains around 25 to 30 visual aids, most of them in color. In this way, the new documentation seeks to reduce reader fatigue and make information more easily digestible.
For example, quality control is a vital aspect of the role of technologists. The team behind the updates wanted to clearly highlight how quality control works, so they included images to demonstrate this visually. Numerous illustrations of clinical cases and illustrations and pictures to demonstrate artifacts in SPECT convey difficult concepts in a visually appealing way to enable the reader to understand the concepts easily
Focus on new camera technology
Nuclear imaging has principally used the same technology for over 50 years. However, the last decade has seen the release of brand new camera designs and imaging technologies.
Significant camera hardware advances from Anger-based camera technology to solid-state nuclear imaging have been highlighted in detail in these new guidelines. Solid-state camera systems provide more advanced technology and benefits over Anger cameras such as being cardiac focused with higher resolution, sensitivity, and higher quality images.
The guidelines have been updated to show the physical principles of these cameras and explain what they can do. The guidelines for how to read images from these newer cameras are a vital part of this explanation.
A complete review of suggested protocols and radioisotope dosings to use for cardiac SPECT imaging is available in the new guidelines. The newer solid-state cameras are capable of acquiring high-quality diagnostic images at much faster speed and lower isotope doses – cutting back radiation and speeding up the test for the patient.
Newer aspects of image interpretation
Attenuation correction to correct for decreased counts is yet to be widely adopted for SPECT image interpretation. This is the mechanism through which soft tissue artifacts are removed from SPECT imaging. The new guidelines have a focussed section on how clinicians should use attenuation correction for interpretation of SPECT scans.
The new guidelines highlight how attenuation correction should be performed, what artifacts should be avoided, and how they can be recognized and corrected. Ultimately, the goal is to reduce the impact of attenuation in order to provide images that are more uniform and allow for higher reading confidence.
There is an entirely new section in the updated guidelines that covers patient-centered imaging. ASNC has strongly advocated for tailoring of imaging for the individual patient and reducing radiation. While a one-test-fits-all approach may simplify clinical decision-making, it is suboptimal for patient care. From their guidelines:
“The key principles of the desirable individualized imaging approach include justification, that is, appropriate testing, and optimization, i.e., performing the test in an ideal manner.”
The focus should be on the patient rather than the protocol and performing the test in a way that will be best for the individual. This section of the guidelines includes strategies for reducing the use of radiation and guidelines for choosing the correct protocol. It all ties back to the “right test for the right patient” message that was central to the update.
Development and use of guidelines
The guidelines were developed over a period of time and underwent updates as they went through rounds of peer reviews and the committee. In this way, the process to develop the guidelines was rigorous.
Dr. Ananthasubramaniam was excited to see the results of this team work of experts go live. The ASNC SPECT guidelines form the backbone of guidance to physicians and technologists and serves as an updated reference for many questions. He trains many cardiology fellows per year and uses these guidelines as the main document from which to train them. It is his belief that the new guidelines are an important document that will help clinicians to perform better SPECT imaging and ultimately, help patients too.
Today’s SPECT technology effectively allows for exceedingly low radiation dose imaging and personalized imaging protocols. The updated SPECT guidelines look into the future by discussing the promise of myocardial blood flow quantitation with the advent of the newer camera systems. By leveraging the new advancements, the revised guidelines promote a more patient-centric and personalized approach that contributes to higher-quality imaging and more meaningful results.
The medical community considers the update a significant move toward the standardization of SPECT MPI and one that will ultimately allow them to provide patients with the highest level of customized care.
The role and future of SPECT
Dr. Ananthasubramaniam believes the role of SPECT is expanding. While PET is making some inroads, SPECT is the predominant technology driving cardiology imaging today worldwide.
For example, in the past, SPECT was only for coronary artery disease, but it is now making its way into other pathologies. Now you are seeing SPECT used for Cardiac Amyloidosis imaging too.
Overall, there continues to be new technology and new protocols being developed in the SPECT space. Suggestions for how to improve image quality by incorporating specific software such as resolution recovery even with existing Anger cameras are discussed in detail.
The updated guidelines are expected to be valid for quite some time to come as they also include insights into where SPECT is heading. For example, new technology that is not yet fully developed is discussed, such as blood flow quantification.
All in all, the future of SPECT looks bright with much more to come.