Cancer Therapies and Nuclear Material Detection Boosted by Newly Discovered Protein
Scientists at Lawrence Livermore National Laboratory (LLNL) and Penn State demonstrated how a protein can be recovered and purified for radioactive metals like actinium that could be beneficial for both next-generation drugs used in therapies against cancer and the detection of nuclear activities.
Radioactive metals occupy a unique and essential place in a variety of medical and therapeutic imaging applications, but they require lengthy separation processes for their purification, as well as synthetic and expensive chelators (molecules adapted to bind radioactive metal ions ) which must form exceptionally stable complexes. in the patient to minimize toxicity. Actinium-based therapies could revolutionize cancer medicine, with treatment effectiveness hundreds of times greater than current drugs. However, they remain out of reach due to difficulties throughout the actinium supply chain, from isotope production to the study of element chemistry and the development of robust chelators for that. -this.
“These challenges exist even for relatively widely used medical isotopes, such as radioactive yttrium, but they are even more painful in the case of actinium,” said Gauthier Deblonde, LLNL scientist, lead author of a article published in Scientists progress.
Actinium turns out to be one of the rarest elements naturally present on Earth, and its medical isotope must be produced in nuclear reactors or other large and expensive instruments. As such, actinium chemistry is among the least understood, hampering the development of actinium-based medical applications. Research efforts have so far focused on the reuse or adaptation of known synthetic molecules used in the field of nuclear chemistry, but results have been limited with actinium. The new research took a radically new approach and took advantage of a natural protein, lanmodulin, discovered by members of the Penn State team in 2018. This new strategy not only improves and simplifies the purification processes of the lanmodulin. ‘actinium, but can also be used to recover and detect other radioactive elements, even at extremely low levels.
The team showed how lanmodulin can be used to bind, recover and purify actinium (at least 99.5% purity achieved in one step), as well as another medically relevant radioisotope, yttrium -90, which is used for the treatment and diagnosis of cancer. The unprecedented efficiency and simplicity of the protein-based approach also makes it possible to prepare actinium at a much lower cost and to probe its chemistry more conveniently. The process is also likely to be extended to many other radioactive isotopes used in radiation therapy and imaging.
“Our new technique represents a paradigm shift not only in the development of actinium chemistry and actinium-based pharmaceuticals, but also in nuclear medicine more generally,” said the co-corresponding author and assistant professor of chemistry at Penn State, Joseph Cotruvo Jr.
The actinium-lanmodulin complex is the very first actinium protein to be characterized. Researchers have found that lanmodulin is so efficient compared to conventional molecules that it binds specifically to actinium even in the presence of large amounts of process impurities, like radium and strontium, or physiological elements like calcium, zinc, copper and others. The study also shows that the protein is more efficient at binding actinium than at binding rare earth elements, the metals to which it binds in nature.
“Our approach, which combines the tight and specific binding of lanmodulin with inexpensive filtration devices, has allowed us to easily access minute amounts of radiometals, as low as a few attograms, where traditional technologies based on Synthetic chelators fail, ”Deblonde said. “What we accomplished here was just unfathomable a few years ago. The unique combination of radiochemistry, metal separation and biochemistry skills at LLNL and Penn State has made it possible. I think our technology will be incredibly useful no only for nuclear medicine, but also for field analysis of radioactive samples. An attogram is one billionth of a billionth of a gram, or about the weight of a single viral particle. In this case, it is the weight of ‘barely about 3000 actinium atoms.
The research not only offers insight into the basic chemistry of actinium, but also suggests that the actinium-lanmodulin complex could be the basis for new actinium-based pharmaceuticals, as it outperforms small chelators in many ways. metals currently used in clinical and clinical trials.
“We believe our results unify the fields of metal separation and biochemistry and have great potential to revolutionize several critical steps in medicinal chemistry, from isotope purification to the delivery of therapeutic doses to patients,” said said Cotruvo.
Other Livermore researchers include Ziye Dong, Paul Wooddy, and Mavrik Zavarin, in addition to Joseph Mattocks at Penn State.
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Gauthier J.-P. Deblonde et al, Capturing an elusive but critical element: the natural protein enables the chemistry of actinium, Scientists progress (2021). DOI: 10.1126 / sciadv.abk0273. www.science.org/doi/10.1126/sciadv.abk0273
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