Diagnostic Imaging Procedures

You may have heard the term theranostics when reading about cancer treatments, but what does it mean? The word theranostics is a combination of the words “therapy” and “diagnostics,” and theranostics does just that. It uses radioisotopes to first image a patient’s tumor for diagnostics and then therapeutically treat that tumor.

We spoke with Charles Manning, Ph.D., a cancer systems imaging researcher, to learn more about how theranostics works.

What are radioisotopes?

Theranostics relies on radioisotopes, which are unstable variants of elements, sometimes also called radionuclides, radiopharmaceuticals or radiotracers. “We have a potpourri of radioisotopes that apply to both the imaging and the therapeutics,” Manning says.

Radioisotopes release radiation to become more stable, which is called radioactive decay. Both the diagnostic and the therapeutic parts of theranostics take advantage of the radiation that radioisotopes give off.

Using radioisotopes for diagnostics

In the diagnostics half of theranostics, clinicians use radioisotopes for precision imaging of tumors. “Every patient who comes to MD Anderson has unique features about their tumors,” says Manning. “Radiopharmaceuticals allow us to quantify and characterize those features non-invasively. This helps us understand what treatment options would be best for a patient before we treat them.”

So how are radioisotopes used for diagnostic imaging? Researchers identify a target on the surface of cancer cells and a molecule that will find and bind to that specific target. Then, they link the targeting molecule with a radioisotope to form the diagnostic molecule.

Patients receive the diagnostic molecule via an infusion. Once inside a patient, it makes its way to the cancer cells and attaches to them. Then, clinicians use an imaging scan, usually positron emission tomography (PET), to detect the radioactive decay that the radioisotope half of the diagnostic molecule emits.

“Many of the patients who undergo theranostics treatment already have a cancer diagnosis, so we know the locations of their tumors,” notes Manning. “So, we're asking other questions with theranostics imaging.” Those questions include:

• How quickly do the diagnostic molecules make it to the tumor and how long do they stay there?
• What fraction of the diagnostic molecules that were injected make it there?
• If there are multiple tumors, does the diagnostic molecule target all of them, ensuring that they could also be treated?

The answers to these questions help determine if the targeting molecule is a good treatment option for a patient.

Using radioisotopes for therapy

“If the diagnostic imaging shows that the selected cancer cell target is a good match for the patient’s tumors, they'll then be treated with the therapeutic molecule,” Manning continues.

To create the therapeutic molecule, scientists take the same piece of the diagnostic molecule that finds and binds to a target on the cancer cell surface and attach it to a different radioisotope. “Theranostics is unique in that it lets us swap the radioisotope that allows diagnostic imaging for one that will kill the cancer cells,” explains Manning. The therapeutic molecule is then administered via infusion and makes its way to the cancer cells.

The radioactive decay that the radioisotope gives off damages the cancer cells and their DNA, but it serves a dual purpose. “We can visualize that radiation, too, which allows physicians to follow the therapy directly, noninvasively and quantitatively,” Manning says. “We can measure how much of the therapeutic molecule got there, which is unique to theranostics.”

Side effects of theranostics

Radioisotopes have a characteristic called their half-life. The half-life is how long it takes for half of the total number of unstable radioisotope molecules to decay into more stable molecules that don’t give off radiation.

Diagnostic radioisotopes have short half-lives, typically about an hour, so they only remain in a patient’s system for a short time. Therapeutic radioisotopes usually have a half-life of three to seven days.

“Since the therapy half of theranostics is all about delivering radiation to the tumor, we actually prefer that the therapeutic radioisotopes stay in the tumor tissue and deliver their dose of radiation over a longer period,” Manning says.

“Unlike more traditional treatments, the total amount of radiation that's administered is quite low,” explains Manning, “and the radiation is directly targeted to the cancer cells, which reduces side effects.” Still, some organ systems are particularly sensitive with respect to radiation, so physicians continue to monitor carefully for potential toxicity and side effects like fatigue, anemia and nausea.

What’s next in theranostics research

Theranostics approaches are currently approved for use in neuroendocrine and prostate cancers. “In our research endeavors at MD Anderson, we're highly motivated to find ways to deliver this approach to patients with other types of tumors or other disease sites that do not yet benefit,” says Manning.

One area of interest, especially for therapeutics, is alternative or improved radioisotopes. When different radioisotopes undergo radioactive decay, they produce different types of radiation, such as alpha or beta particles. “The types of radiation that we can achieve with various radioisotopes give us opportunities to tailor the therapeutics molecule to the biology of individual tumors,” says Manning.

For example, alpha particles are extremely potent, but they can only travel a very short distance. We can take advantage of this by attaching a radioisotope that gives off alpha particles to a targeting molecule that quickly moves from the cell surface to the inside of the cell. There, the alpha particles produced by the radioactive decay are close enough to damage the cancer cell DNA, despite their short range.

In addition to new and improved radioisotopes, scientists are also researching different biological targets for the theranostics molecules to attach to. A good target candidate is abundant on the surface of cancer cells but not on the surface of healthy cells. “We are very fortunate at MD Anderson to benefit from prior efforts that have characterized the surfaceome of many solid tumors, meaning what proteins are on the cancer cell surface,” Manning says. “We have hundreds to even thousands of clinical specimens that make this research possible.”

Theranostics at MD Anderson

“We're now onboarding a research and development program focused on radioisotope theranostics that aims to be bench to bedside, taking new radioisotopes from their creation in the lab all the way to use in patient treatment,” Manning says. “This is truly unique to MD Anderson. There are not a lot of academic institutions that could pull this off.”

While our patients benefit from having a radiochemistry facility on campus that produces radioisotopes, MD Anderson’s culture also plays a significant role. “One of the biggest assets that we have here at MD Anderson is being able to partner with our clinicians early on in the process when we are developing new theranostic approaches,” says Brooke Graham, director of Research Planning and Development in the Center for Advanced Biomedical Imaging. “It allows us to swiftly move new breakthroughs and discoveries into clinical trials to benefit patients.”

“The physicians who see our patients on a daily basis are supported so strongly by our basic science researchers,” Manning adds. “The direction of our theranostics research at MD Anderson is completely determined by unmet clinical needs.”

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