Sep 27, 2019

Ep 196: Rose Boll - Group Leader, Medical, Industrial, & Research Isotopes, ORNL

Group Leader, Medical, Industrial, & Research Isotopes
Oak Ridge National Laboratory
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Show notes

Rose’s journey to Oak Ridge (1:10)
1:10-7:33 (Rose explains how she progressed from a chemistry student to a Group Leader at Oak Ridge National Laboratory.)

Q. Where did you grow up and how did you get interested in isotopes?
(1:25) A. Rose grew up in southern Ohio along with 10 brothers and sisters. Rose studied biology and chemistry in college before working in hospital laboratories where she became interested in medical isotopes. Rose then attended graduate school at the University of Tennessee to study organic chemistry and focused on radioisotopes. She then went on to a postdoctoral position at Oak Ridge National Laboratory where she has worked on a project to recover Actinium-225 and Thorium-229, which are used in targeted alpha therapy. She is now the Group Leader of Medical, Industrial, & Research Isotopes at Oak Ridge National Laboratory.

Rose has always enjoyed science and math. While Rose had planned on attending medical school, she decided she would rather take chemistry than biology classes. The hospital lab work, however, enabled Rose to study both medicine and chemistry. Rose’s love of science stems primarily from her father who worked in refrigeration and taught Rose about freons as she was growing up.

The Actinium-225 isotope (7:34)
7:34-16:29 (Rose defines what an isotope is. She also explains what Actinium-225 is and the Tri-Lab Project that produces it.)

Q. What is an isotope?
(7:57) A. An isotope is a form of an atom that has a different number of neutrons. For example, Sodium-22 and Sodium-24 are both Sodium atoms, but have differing neutron amounts. A different number of neutrons means that some isotopes will decay at different rates and with alpha particles, beta particles or gamma energy.

At the point Rose joined Oak Ridge, the laboratory was recovering Thorium-229 from waste material left over from the production of Uranium-233. Uranium-233 is a fissile isotope, meaning it can be used to produce bombs. Thorium-229 has a half-life of 7,000 years, meaning it takes a long time for the isotope to decay. Actinium-225 is a product of Thorium-229 decay and only has a decay rate of 15 days. Actinium-225 is used in cancer treatment as a targeted alpha therapy isotope.

Twenty years ago, Actinium-225 was obtained only through the decay of Thorium-229. More Actinium-225 is needed to meet medical demand, therefore researchers are finding other ways to produce Actinium-225. Researchers are currently using an accelerator to hit a target of Thorium-232 with protons, neutrons or electrons to produce a material that transitions to become Actinium-225.

The Oak Ridge lab does not have an accelerator, but it is part of the Tri-Lab Project that also involves the Los Alamos and Brookhaven national laboratories. Oak Ridge’s role involves the purifying of Actinium-225 from the Thorium-232 target used in Brookhaven. The Project is currently working on moving into Phase 3, which will produce the expected demand of Actinium-225 for the medical industry. Once the research is completed and the method is known, lowering cost of production, the private sector will take over.

A global collaboration (16:30)
16:30-22:11 (Rose explains that available equipment determines what theories are tested. She also discusses that this is a global collaboration.)

Q. Can you walk us through the phases of establishing this research method?
(16:58) A. Phase 1 began with testing the theory of producing Actinium-225. This involved irradiating the target (a thin metal sheet of Thorium-232) and analyzing the results. For the Tri-Lab Project, the available tools and equipment dictated the primary method tested. Accelerators and other necessary tools are expensive, but the promising first results justified the investment.

There are other labs around the world with accelerators that are researching the same method of Actinium-225 production. This is needed if the medical industry’s demand increases globally. Conferences enable a strong collaboration in the creation of the targeted alpha therapy for cancer treatment.

The demand for Actinium-225 (22:12)
22:12-27:19 (Rose explains the cause of the demand for Actinium-225. She also explains that, unlike antibiotics, people generally do not build a tolerance to radioisotopes.)

Q. What is the reason for the Actinium-225 demand?
(21:53) A. The application for targeted alpha therapy for different cancers have been showing positive results. This includes targeting metastasized cancers with radiation as well as targeting Leukemia cells, HIV cells and certain fungal infections resistant to antibiotics with radioisotopes. The application is becoming more broad as it is adopted for different cancer types.

Rose has not heard that radiation resistance is prevalent but some people can be more tolerant to radiotherapy than others. There may not be enough evidence of treating the same patient multiple times to see if they have developed immunity to the therapy.

Medical isotope regulation (27:20)
27:20-32:06 (Rose discusses how medical isotopes are regulated.)

Q. Are medical isotopes already regulated?
(28:07) A. There are different levels of regulation based on the various research stages. Rose’s studies undergo less regulation than clinical trials involving humans. The regulations that Rose’s team must abide by require the Actinium-225 to be pure before it can be used in medication. This means obtaining the FDA’s Current Good Manufacturing Practices (CGMP) standards.

The phase of Actinium-225 production depends on the specific cancer treatment. Lukiama has been working on trials for several years and is approaching Phase 3, while some breast cancer studies are in the early phase of looking at effects on mouse cells. Rose is not involved in a particular trial phase because Oak Ridge focuses on isotope production for medication manufacturing, but is currently setting up CGMP, which they hope to have in place by next year.

Challenges of Actinium-225 production (32:07)
32:07-43:23 (Rose discusses the difficulties encountered in the project. She also explains why the private sector will not be able to take over the project for another 5 to 10 years.)

Q. What were the longest or most difficult parts of the project to overcome?
(32:40) A. Recovering the initial Thorium material was the most difficult part of the project as the waste was mixed. As the demand for Actinium-225 increased, meeting the needs of the customers became the next difficult step of the project. This required the team to shift away from a research and development mindset and towards one where they could produce enough Actinium-225 at a high purity level to meet the weekly needs of the customer.

Measuring the purity is also challenging because one millicurie (a radioactive measurement, mCi) of Actinium-225 has a mass of only 0.2 nanograms. This amount is impossible to detect with the eye, but a geiger counter is still able to detect the radioactivity. Vials containing this amount of Actinium-225 are shipped through regular mail services, but there are regulations in place that ensure the radiation is contained.

Using other sources of waste is not possible for this particular isotope. The original Uranium-233 was produced at Oak Ridge National Lab. Additionally, the role of the lab is not to produce for the private sector, but to research and develop until a project can be handed off to the private sector. The project is getting close to entering Phase 3, where they hope to produce 100mCi per target, which approaches the needed curie production level for widespread application of targeted alpha therapy. This level of production is also needed for the private sector to be able to afford the needed facilities that must be designated solely to the production of Actinium-225. Rose predicts this may take 5 to 10 years.

The project is working to increase the yield. In the early stages, the power of the beam and the length of time of radiation was adjusted. The same parameters are then used on larger targets during production and the beam time and the amount of energy used is then optimized to produce higher quantities.

Radioisotope education (43:24)
43:24-56:54 (Rose explains her role as an educator and why she believes teaching children about radioisotopes is important.)

Q. Are these some of the same topics that you teach?
(43:52) A. Rose taught at the University of Tennessee for 10 years before joining Oak Ridge full time and still occasionally guest lectures in radiochemistry classes. The lab also has interns, many of whom are undergraduate, graduate and postdoctoral students that Rose works with.

Rose used to teach chemistry and would give lectures on isotopes. She believes educating her students about radiation made them more informed voters. Rose specifically taught the history of radiation and how isotopes are used in various industries. Rose believes that radiation education could easily be incorporated into elementary and high school science classes today to make people more comfortable with radiation. However, some teachers have not been exposed to radioisotope education themselves, making this process difficult. Despite this, Rose has seen an improvement in radiation education since she was a child. She has seen a decrease in the concern about nuclear explosions, which Rose believes may be because the younger generation is exposed to more technology today than prior generations.

The future of medical isotopes (56:55)
56:55-1:01:26 (Rose explains how her views of the nuclear industry changed over time. She also discusses her hopes for the future of medical isotopes and her role in the industry.)

Q. How has your impression of the nuclear industry changed over time?
(57:25) A. When Rose was graduating high school, there was a strong anti-nuclear GreenPeace movement. Rose remembers agreeing with them because she wanted to be environmentally sound. However, her education in radiochemistry taught her that the ideas of the time were not necessarily correct.

Moving forward, Rose wants people to realize the benefit of medical isotopes. Radioisotope treatment is becoming more of an option for people, and Rose believes education is important in achieving this.

For Rose’s work specifically, she is looking forward to improving the techniques used to separate materials to increase purification and manufacturing standards. Rose is coming to the end of her career and sees her future role becoming primarily involved with education.

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