GoKawiilIn the 1940s, as Los Alamos scientists raced to unlock and harness the physics of fission, a parallel scientific revolution was taking shape, one that would take nuclear science from splitting atoms to saving lives: biomedical isotopes.
The science of isotopes was fundamental to the mission at Los Alamos from day one. Some isotopes fission readily, like the uranium used in nuclear reactors (U-235), while others don’t, like the uranium found in nature (U-238). The difference boils down to neutrons. Isotopes of a given element have the same number of protons (92 for uranium), but different numbers of neutrons (143 for U-235 and 146 for U-238), meaning they behave the same chemically but differ in mass or radiation emissions.
These differences mean both stable and unstable isotopes can be used as labels. Stable isotope mass measurements can be compared to identify the ratio of particular isotopes that is present. Unstable isotopes emit radiation that can be detected. These characteristics make isotopes powerful, nondisruptive tracers and probes for living systems. As Manhattan Project scientists formed a deep practical understanding of isotope separation, enrichment, and measurement methods, visionary researchers saw vast potential in biomedicine. Through the 1940s and 1950s, Lab scientists turned that understanding from wartime nuclear physics toward broad, exploratory science.
Stable isotopes
Los Alamos was one of the world’s first producers of enriched stable isotopes, which are useful as nonradioactive molecular tracers. When measured as ratios of heavy to light, like carbon-13 to carbon-12, stable isotopes can reveal information about metabolic or pathologic processes. They can also be used to selectively strengthen otherwise weak atomic signals, allowing new types of nuclear measurements.
Carbon-13, for example, was essential to the development of nuclear magnetic resonance (NMR) spectroscopy, which enables today’s magnetic resonance imaging (MRI) and a slew of other applications in which precise, non-destructive chemical and structural measurement is needed. Carbon-12 is the dominant form of carbon in nature, but because it has no magnetic moment, it’s invisible to NMR, which uses magnetic field maneuvers to detect certain nuclei. So, to make biochemicals measurable by NMR, some of their carbon-12 atoms have to be replaced with carbon-13, which has an unpaired nuclear particle, giving its nucleus a magnetic moment and making it visible to NMR. Throughout the 1950s, Los Alamos advanced both the science and the supply chain that took NMR from a physics curiosity to a cornerstone technique in chemistry, biology, and medicine. Other key spectroscopic, or molecular-interaction, techniques developed during this time that relied on Los Alamos–made stable isotopes include Raman spectroscopy, electron spin resonance, and surface plasmon resonance.
Throughout the 1950s, Los Alamos advanced both the science and the supply chain that took NMR from a physics curiosity to a cornerstone technique in chemistry, biology, and medicine.
During the 1970s and 1980s, Los Alamos pioneered the large-scale isolation of stable isotopes using enormous distillation columns, the largest extending down nearly 700 feet into the ground. The columns were so tall because they used evaporation and condensation to physically separate isotopes by mass, but because the mass difference was so slight—just one neutron—it took many cycles of inching the lighter isotopes toward the top and the heavier isotopes toward the bottom to get adequately pure populations. For more than 20 years, the Lab was home to the National Institutes of Health’s Stable Isotope Research Resource, which supported frontier research in basic biology and biomedicine. While production of stable isotopes at Los Alamos has dwindled, having been successfully transitioned to industry, production of unstable isotopes, or radioisotopes, continues in force today and powers vital medical imaging and treatment on a global scale.
Unstable isotopes
Radioisotopes decay at predictable rates, becoming other isotopes or even other elements, by emitting different types of radiation. It’s the radiation that enables medical imaging and therapy. Rubidium-82 (Rb-82), for example, is used in cardiac PET (positron emission tomography) imaging and allows real-time visualization of blood flow and heart function. But Rb-82 is short-lived, lasting just over a minute. So, the trick is to start with strontium-82 (Sr-82), also a radioisotope but one that lasts weeks rather than minutes. The pathway goes like this: unstable Sr-82 converts a proton into a neutron and emits a neutrino, thus becoming Rb-82; Rb-82 is also unstable and converts another proton into a neutron, emits another neutrino and a positron, and stops decaying as a stable isotope of krypton. The emitted positron is what enables medical imaging, but because Rb-82 decays so quickly, it has to be produced onsite from a Sr-82 source as needed for PET imaging. The ability to produce, purify, and distribute large quantities of Sr-82 fundamentally changed how coronary artery disease is diagnosed and managed, and Los Alamos made it happen.
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