Ellen Phiddian
Cosmos science journalist
The super-rare radioactive heavy metal actinium is a promising treatment for some cancers.
But, until now, actinium’s rarity and radioactivity has made it a very difficult element to study.
US chemists have fixed actinium atoms in place long enough to get a detailed picture of how they bind to other molecules.
They have published their findings today in Nature Communications.
“We’ve achieved a really technically difficult experimental method that pushes the boundaries of isotope chemistry and lets us gain a better understanding of this element,” says Associate Professor Rebecca Abergel, leader of the heavy element chemistry group at the Lawrence Berkeley National Laboratory, US.
Actinium is a radioactive element with an atomic number of 89. It only appears naturally in very small amounts in uranium ores. When used in research, it’s usually made in a lab by bombarding another element, radium.
One isotope (atoms with a specific mass) of actinium, actinium-225, is being tested in clinical trials for a new type of cancer treatment called targeted alpha therapy.
This treatment involves binding a radioactive atom to a biological molecule, like a protein, which is drawn to the cancer site. As the atom decays, it releases particles that destroy the nearby cancer cells, but don’t travel far enough to damage the rest of the body.
“There’s a breadth of applications for these elements, from nuclear energy to medicine to national security, but if we don’t know how they behave, that inhibits the progress we can make,” says first author Dr Jen Wacker, a chemist at Berkeley.
“There’s a movement to design better delivery systems to get the actinium to particular cells and keep it there,” says Abergel.
“If we can engineer proteins to bind the actinium with a really high affinity, and either be fused with an antibody or serve as the targeting protein, that would really enable new ways to develop radiopharmaceuticals.”
In this study, the researchers used a different isotope of actinium, actinium-227, because it’s longer-lived.
They purified 5 micrograms of the metal – 5 millionths of a gram – and then bound the atoms to proteins with the help of molecules called ligands. They allowed this mixture to grow into crystals over a week, developing a “macromolecular scaffold”.
Then, they cooled the crystals with liquid nitrogen and used X-ray crystallography to develop 3D images of the arrangement of atoms.
This is the first time anyone has been able to develop a crystal structure for a compound containing actinium.
“I’ve been working in crystallography for 40 years and seen a lot of things, and the method the team is using is unique and provides details we couldn’t get in the past,” says Dr Marc Allaire, head of the Berkeley Center for Structural Biology team at the Advanced Light Source, where the researchers did the imaging.
“To the best of my knowledge, Berkeley Lab is the only place in the world where we do this kind of study and measure radioactive protein crystals.”
Next, the researchers are planning to look at the therapeutic actinium-225, as well as seeing if they can bind it to other proteins to see how it responds.
“It hopefully will enable us and others to develop better systems that are useful for targeted alpha therapy,” says Abergel.
