Harness Help, Avoid Harm
NASA, NCI Scientists ‘Demystify’ Radiation
What do the sun and cancer treatments have in common? Radiation.
The final Demystifying Medicine lecture of the 2023 season focused on that commonality, featuring NASA heliophysicist Dr. Nicola Fox and National Cancer Institute radiation oncologist Dr. Freddy E. Escorcia.
In a talk titled “Solar Winds and Magic Bullets: Making Our Way in a World of Solar Radiation,” the speakers discussed the radiation at work in our solar system and in earthly cancer treatments.
Defining Radiation’s Power
According to the NCI, radiation is energy released in electromagnetic waves. Common sources include cosmic rays from outer space and medical x-rays. Radiation can slow the growth of cells by damaging their DNA; if the radiation dose is high enough, it can kill cells outright.
On Earth, the closest we get to cosmic radiation is the ultraviolet light (UV) radiation from the sun that reaches us through our planet’s atmosphere. But, out in space, radiation is much more plentiful—and dangerous.
Going to the Source
Fox, associate administrator of the NASA Science Mission Directorate, currently oversees more than 140 missions that enable a deep scientific understanding of Earth and other planets, the sun and our universe. Her lecture described heliophysics and solar radiation.
Heliophysics is the science of understanding the sun and its interactions with Earth and the solar system, including space weather. The sun is a ball of hot plasma heated by nuclear fusion reactions at its core. Its upper atmosphere—the corona—releases a stream of charged particles known as solar wind, which influences the aurora borealis and man-made power grids.
The heliophysics field is only about 60 years old, founded by Fox’s mentor and fellow NASA physicist Dr. Eugene “Gene” Parker. Parker initiated a chain of discoveries leading to the first-ever mission to “touch” the sun. The Parker Solar Probe launched in 2018 and will orbit the sun 24 times, recording data about the flow of energy from the sun.
Radiation in Space
One huge concern for off-planet travelers is radiation exposure. Astronauts in low Earth orbit (such as the International Space Station) are protected from space radiation by Earth’s atmosphere. Beyond that, human explorers are exposed to radiation from particles trapped in Earth’s magnetic field, galactic cosmic rays from beyond our solar system and radiation emitted from the sun.
Exposure is measured in Milli-Sievert (mSv), with one mSv equal to the radiation produced by three chest x-rays. Most missions are generally under 100 mSv, according to Fox, and NASA limits total career exposure to 600 mSv. A mission to Mars would be double the career exposure limit, she estimated.
So, how can NASA protect astronauts as it plans for missions going deeper into space?
Enter the space biology program. Described by Fox as “science enabling exploration and exploration enabling science,” the program seeks to better understand how spaceflight affects living systems. Scientists are currently studying ways to mitigate and protect against radiation.
Back Down to Earth
On Earth, researchers have harnessed the power of radiation beneficially for more than a hundred years in diagnostics and therapy. Wilhelm Röntgen, the “father of radiology,” discovered x-ray radiation in 1895. He and other scientists began using radiation for therapeutic purposes soon after; in 1905, for example, radiation therapy caused dramatic tumor shrinkage in a patient with lymphoma.
These days, Escorcia, a Lasker clinical research scholar and NIH distinguished scholar, heads the Laboratory of Molecular Radiotherapy at NCI’s Center for Cancer Research. His group engineers radioconjugates (a radioactive isotope attached to a targeting agent that seeks out cancer cells) to yield molecular imaging and therapeutic agents for liver cancer.
More than half of all cancer patients receive radiation therapy, which involves aiming a beam of radiation at the tumor. However, “local treatments can only get us so far,” Escorcia said. A patient could have a tumor shrink in one area only to later have metastatic disease develop outside the treated area.
‘Can We Make Something Better?’
Escorcia believes there may be alternatives. He proposed creating a group of drugs dubbed “theranostics”—engineered biomolecules with a radioisotope attached that could double as diagnostic and therapeutic agents. Tumors often have genes that are overexpressed in the diseased tissue. Researchers can identify these genes with gene sequencing and use them as targets for treatments.
How might theranostics work? Escorcia described using it against hepatocellular carcinoma (HCC), the most common type of liver cancer.
To see many cancers, scientists employ positron emission tomography (PET) scans, which use a radioactive tracer that binds to tumors and shows up on the resulting image. PET scans using the commonly used clinical agent, 18-F-fluorodeoxyglucose or FDG, do not work well for liver cancer because the tumors do not usually take up the tracer.
“Maybe liver cancer needs its own imaging agent,” Escorcia realized. He already had a target gene: Glypican-3 (GPC3), which is expressed in 75% to 90% of HCC cases.
Additionally, the traditional treatments for HCC—including delivering radiation-containing microspheres via a catheter in the hepatic artery or with radiation beams—show that HCC is sensitive to radiation. Still, the clinical outcomes of patients with this disease remain poor and more effective treatments are needed. Escorcia decided to build a molecule that would double as an imaging agent and a therapeutic agent.
‘Where the Rubber Hits the Road’
After some trial and error, he settled on a nanobody (similar to an antibody but 10 times smaller) that was specific to GPC3 and attached a radioconjugate to treat the tumor. The nanobody worked well as an imaging agent for PET scanning but it also showed up strongly in the kidneys, which could potentially cause kidney toxicity if it were used for therapy.
Although the GPC3 nanobody needs more fine-tuning to mitigate the kidney toxicity, Escorcia is optimistic about deploying the process to other cancers.
“You could theoretically apply this to any cancer as long as you have the right target,” he said, “and that’s where the rubber hits the road.”
In addition to building new molecules, researchers can also repurpose existing agents. Prostate-specific membrane antigen (PSMA), for example, is a tracer target for PET imaging in patients with prostate cancer. Research from Johns Hopkins University showed that PSMA is also overexpressed in liver cancers and may be another theranostic target for HCC. Escorcia has launched a clinical trial at NCI evaluating whether a PSMA PET imaging agent could be helpful in diagnosing and monitoring treatment response in patients with HCC (https://tinyurl.com/mr33venh).
Putting It All Together
In 2016, the National Center for Advancing Translational Sciences partnered with NASA for the Tissue Chips in Space program. Chips simulating heart tissue, bone and cartilage, muscles, intestines and other organs have traveled to and from space, with the most recent launch on Mar. 14.
Escorcia and Fox also see potential for similar collaboration in making agents that protect against radiation. Patients undergoing radiation therapy can experience unpleasant side effects in healthy tissue around the treated area. This is still an area of active research, but Escorcia thinks it could also be applied to astronauts.
View the archived lecture at https://go.nih.gov/7QwolFp.