Hexbyte Glen Cove ORNL meets key FDA milestone for cancer-fighting Ac-225 isotope thumbnail

Hexbyte Glen Cove ORNL meets key FDA milestone for cancer-fighting Ac-225 isotope

Hexbyte Glen Cove

Targeted alpha therapy can deliver radiation to specific cells, with minimal effect on surrounding, healthy cells. Credit: Michelle Lehman and Jaimee Janiga/ORNL, U.S. Dept. of Energy

A rare isotope in high demand for treating cancer is now more available to pharmaceutical companies developing and testing new drugs.

The U.S. Food and Drug Administration recently acknowledged receipt of Oak Ridge National Laboratory’s drug master file for actinium-225 nitrate, which enables to reference the document to support applications for their own Ac-225-based drugs without disclosing proprietary information. The FDA requires an to have an active drug master file before it will approve products containing that ingredient. This file contains information about Ac-225 derived from thorium-229, including materials used in its preparation, and the current Good Manufacturing Practice processes involved in its production.

ORNL produces Ac-225 for the Department of Energy’s Isotope Program, which then sells it for research and applications. To meet federal missions, facilitate emerging technology, reduce U.S. dependence on foreign supply and promote the country’s economic prosperity and technical strength, the DOE Isotope Program provides critical that are in short supply.

Ac-225, a decay product of thorium-229, is used for targeted alpha therapy treatment for certain types of prostate, brain and neuroendocrine cancers. The high-energy alpha particles it releases can interrupt DNA processes, keeping cancer cells from replicating or even killing them altogether.

But Ac-225 doesn’t occur naturally. ORNL, for the DOE Isotope Program, produces the bulk of the world’s supply.

“The promise of targeted alpha therapy is so great, demand for the radioisotope already outweighs the amount produced,” said ORNL’s Laura Harvey. To augment the supply, the Isotope Program supports the production of Ac-225 through other methods as well, including with the use of accelerators.

Harvey is part of an ORNL team producing Ac-225 from a stockpile of thorium-229 stored at ORNL. A byproduct from past nuclear programs, the thorium material was separated and recovered to build ORNL’s current inventory. Ac-225 is one of the key radioisotopes that occur as the thorium decays.

The thorium-229 stockpile periodically is processed to recover radium-225, which decays to the Ac-225 that is recovered and used in treatment of cancer. The radium-225 that accumulates becomes a secondary source of Ac-225. Each week, the ORNL team harvests Ac-225 for further purification and packaging for shipments that are sent to customers around the world for fundamental research, and treatments.

A purified sample of actinium-225, produced at ORNL’s Radiochemical Engineering Development Center, glows blue when the air that surrounds it is ionized by alpha particles. Credit: ORNL, U.S. Dept. of Energy

“The whole benefit to the radioactive decay is that we don’t have to do anything magical to the thorium to keep it producing Ac-225,” said ORNL’s Paul Benny. “It is a long-lived resource that we can continually harvest.”

The science that allows separation of isotopes is the result of decades of groundbreaking radioisotope separation experiments at ORNL’s High Flux Isotope Reactor and Radiochemical Engineering Development Center, with support from the DOE Isotope Program. ORNL first began work to extract Ac-225 from the thorium stockpile more than two decades ago, sending its first shipment in—to the National Cancer Institute—in 1997.

Meeting the FDA’s current Good Manufacturing Practice requirements for a new active pharmaceutical ingredient typically takes a couple of years, but ORNL and the DOE Isotope Program developed a plan and implemented the requirements in 13 months for its onsite Ac-225 production. Harvey said lab-wide cooperation and support made that timeline possible.

ORNL also made a significant commitment to the Ac-225 effort, providing dedicated hot cell and glovebox space, storage space where materials can be secured and new equipment. The team—which includes technicians, custodians, managers and others—received specialized training for the process.

“Everybody at the lab worked so hard to make sure the Ac-225 had what it needed to move forward,” Harvey said.

That’s because they realize the importance of the work, Benny said. Though Ac-225 is in clinical trials in the United States, other countries already have treated hundreds of cancer patients with Ac-225 and its decay daughter, bismuth-213. The DOE’s Isotope Program manages distribution of the Ac-225 through the National Isotope Development Center.

A patient from Germany who had benefited from treatments with ORNL-produced Ac-225 went to the trouble to contact one ORNL scientist who was involved in earlier Ac-225 production, to thank her and let her know how his life had improved because of ORNL’s efforts.

“Team members know some of the shipments are going directly to patients all over the world,” Benny said. “It’s exciting when you realize what we do matters and has a direct impact on people’s lives. It can make a difference, when you can give people hope and the tools to fight cancer.”

ORNL meets key FDA milestone for cancer-fighting Ac-225 isotope (2021, March 26)
retrieved 28 March 2021
from https://phys.org/news/2021-03-ornl-key-fda-milestone-cancer-fighting.html

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Hexbyte Glen Cove Magnetism meets topology on a superconductor's surface thumbnail

Hexbyte Glen Cove Magnetism meets topology on a superconductor’s surface

Hexbyte Glen Cove

An illustration depicting a topological surface state with an energy band gap (an energy range where electrons are forbidden) between the apices of the top and corresponding bottom cones (allowed energy bands, or the range of energies electrons are allowed to have). A topological surface state is a unique electronic state, only existing at the surface of a material, that reflects strong interactions between an electron’s spin (red arrow) and its orbital motion around an atom’s nucleus. When the electron spins align parallel to each another, as they do here, the material has a type of magnetism called ferromagnetism. Credit: Dan Nevola, Brookhaven National Laboratory

Electrons in a solid occupy distinct energy bands separated by gaps. Energy band gaps are an electronic “no man’s land,” an energy range where no electrons are allowed. Now, scientists studying a compound containing iron, tellurium, and selenium have found that an energy band gap opens at a point where two allowed energy bands intersect on the material’s surface. They observed this unexpected electronic behavior when they cooled the material and probed its electronic structure with laser light. Their findings, reported in the Proceedings of the National Academy of Sciences, could have implications for future quantum information science and electronics.

The particular compound belongs to the family of iron-based , which were initially discovered in 2008. These materials not only conduct electricity without resistance at relatively higher temperatures (but still very cold ones) than other classes of superconductors but also show magnetic properties.

“For a while, people thought that superconductivity and magnetism would work against each other,” said first author Nader Zaki, a scientific associate in the Electron Spectroscopy Group of the Condensed Matter Physics and Materials Science (CMPMS) Division at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory. “We have explored a material where both develop at the same time.”

Aside from superconductivity and magnetism, some iron-based superconductors have the right conditions to host “topological” surface states. The existence of these unique electronic states, localized at the surface (they do not exist in the bulk of the material), reflects between an electron’s spin and its orbital motion around the nucleus of an atom.

“When you have a superconductor with topological surface properties, you’re excited by the possibility of topological superconductivity,” said corresponding author Peter Johnson, leader of the Electron Spectroscopy Group. “Topological superconductivity is potentially capable of supporting Majorana fermions, which could serve as qubits, the information-storing building blocks of quantum computers.”

Quantum computers promise tremendous speedups for calculations that would take an impractical amount of time or be impossible on traditional computers. One of the challenges to realizing practical quantum computing is that qubits are highly sensitive to their environment. Small interactions cause them to lose their quantum state and thus stored information becomes lost. Theory predicts that Majorana fermions (sought-after quasiparticles) existing in superconducting are immune to environmental disturbances, making them an ideal platform for robust qubits.

Seeing the iron-based superconductors as a platform for a range of exotic and potentially important phenomena, Zaki, Johnson, and their colleagues set out to understand the roles of topology, superconductivity and magnetism.

CMPMS Division senior physicist Genda Gu first grew high-quality single crystals of the iron-based compound. Then, Zaki mapped the electronic band structure of the material via laser-based photoemission spectroscopy. When light from a laser is focused onto a small spot on the material, electrons from the surface are “kicked out” (i.e., photoemitted). The energy and momentum of these electrons can then be measured.

When they lowered the temperature, something surprising happened.

“The material went superconducting, as we expected, and we saw a superconducting gap associated with that,” said Zaki. “But what we didn’t expect was the topological surface state opening up a second gap at the Dirac point. You can picture the energy band structure of this surface state as an hourglass or two cones attached at their apex. Where these cones intersect is called the Dirac point.”

As Johnson and Zaki explained, when a gap opens up at the Dirac point, it’s evidence that has been broken. Time-reversal symmetry means that the laws of physics are the same whether you look at a system going forward or backward in time—akin to rewinding a video and seeing the same sequence of events playing in reverse. But under time reversal, electron spins change their direction and break this symmetry. Thus, one of the ways to break time-reversal symmetry is by developing magnetism—specifically, ferromagnetism, a type of magnetism where all electron spins align in a parallel fashion.

“The system is going into the superconducting state and seemingly magnetism is developing,” said Johnson. “We have to assume the magnetism is in the surface region because in this form it cannot coexist in the bulk. This discovery is exciting because the material has a lot of different physics in it: superconductivity, topology, and now magnetism. I like to say it’s one-stop shopping. Understanding how these phenomena arise in the material could provide a basis for many new and exciting technological directions.”

As previously noted, the material’s superconductivity and strong spin-orbit effects could be harnessed for quantum information technologies. Alternatively, the material’s magnetism and strong spin-orbit interactions could enable dissipationless (no energy loss) transport of electrical current in electronics. This capability could be leveraged to develop electronic devices that consume low amounts of power.

Coauthors Alexei Tsvelik, senior scientist and group leader of the CMPMS Division Condensed Matter Theory Group, and Congjun Wu, a professor of physics at the University of California, San Diego, provided theoretical insights on how time reversal symmetry is broken and magnetism originates in the surface region.

“This discovery not only reveals deep connections between topological superconducting states and spontaneous magnetization but also provides important insights into the nature of superconducting gap functions in iron-based superconductors—an outstanding problem in the investigation of strongly correlated unconventional superconductors,” said Wu.

In a separate study with other collaborators in the CMPMS Division, the experimental team is examining how different concentrations of the three elements in the sample contribute to the observed phenomena. Seemingly, tellurium is needed for the topological effects, too much iron kills superconductivity, and selenium enhances superconductivity.

In follow-on experiments, the team hopes to verify the time-reversal symmetry breaking with other methods and explore how substituting elements in the compound modifies its electronic behavior.

“As materials scientists, we like to alter the ingredients in the mixture to see what happens,” said Johnson. “The goal is to figure out how superconductivity, topology, and magnetism interact in these complex materials.”

More information:
Nader Zaki et al. Time-reversal symmetry breaking in the Fe-chalcogenide superconductors, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2007241118

Magnetism meets topology on a superconductor’s surface (2021, March 17)
retrieved 17 March 2021
from https://phys.org/news/2021-03-magnetism-topology-superconductor-surface.html

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