Cancer > Theranostics: Old Tech, New Tricks

Theranostics: Old Tech, New Tricks

Combining therapeutics and diagnostics, Mayo Clinic is building on technologies of the past to design the next generation of radiopharmaceutical therapies.

By Alison Caldwell, Ph.D. Photography by Paul Flessland Illustrations by Tim West

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Oncologist Oliver Sartor, M.D., remembers the exact moment that changed his career. In 1993, he was working in oncology, focusing on experimental trials for treating prostate cancer.

“Experimental cancer medicine is a struggle,” he says. “It’s not easy to go out and cure cancer. It’s hard work, with a lot of opportunity for failure.”

At a conference, he met a nuclear chemist who held the patent for a radioactive isotope of the element samarium, a silvery metal. “He told me, ‘I’m going to take this radiation and put it right on the tumor in the bone where the cancer is,’” recalls Dr. Sartor.

Dr. Sartor was shocked — he couldn’t under-stand how the radiation could target the cancer so precisely. But then the chemist explained that the radioactive isotope known as samarium 153 had a structure that would cause it to bind within tumors of metastatic bone cancer. Once attached, the isotope would decay, releasing radiation directly into the tumor.

It was a eureka moment.

“That was my introduction to theranostics,” says Dr. Sartor. Since that moment, he’s been on a decades-long journey into the field, working on developing therapies that are more precisely targeted and more powerful. Now, he’s part of a dedicated team of researchers and clinicians who are expanding our knowledge about theranostics and working to magnify their use and reach in cancer care.

An Opportunity to Be Truly Bench-to-Bedside

Mayo Clinic is the highest-volume radiopharmaceutical practice in the world. “We treat more than two times as many patients as the next largest practice,” says Geoffrey Johnson, M.D., Ph.D. And he should know — he’s leading the charge working to bring new technologies, studies and experts such as Dr. Sartor to Mayo Clinic.

For Dr. Johnson, his career path led him to nuclear medicine as his specialty because he saw so much potential in theranostics for cancer care.

“It involves all the kinds of technologies that I like,” he says. “This brings together my background in chemistry and my love of advanced nuclear physics, along with advanced scanning technology, to let me develop new imaging technologies and therapy options that we couldn’t have imagined before. I get to work on developing new drugs, running clinical trials and applying my clinical expertise to patient care.”

So far, he’s seen his instinct prove true: Theranostics are becoming a topic of increasing interest in cancer care with new drugs approved in the last decade for neuroendocrine tumors and prostate cancer.

He also sees Mayo Clinic as a key player in the field. Mayo Clinic is the only National Cancer Institute-Designated Comprehensive Cancer Center with integrated yet distinct campuses across three states. All sites are also Society of Nuclear Medicine & Molecular Imaging-designated Comprehensive Radiopharmaceutical Therapy Centers of Excellence.

“Theranostics aren’t an option that we ‘also’ have,” says Dr. Johnson. “They’re integrated into our cancer center, and our approach to cancer care.”

What's in a Name

Theranostics, also called theragnostics, is a blending of the words “therapeutics” and “diagnostics,” and in oncology, it refers to the use of radioactive drugs that can target specific molecules on tumor cells. The radioactive component of the drug, called a radioisotope, can emit low levels of radiation, allowing clinicians to find the locations of tumors using a positron emission tomography (PET) scanner (diagnostics), or they can emit higher levels of radiation to kill the cancer cells they bind to (therapeutics). This allows doctors to use the same targeting molecule to both image and kill cancer cells.

“Being able to see the tumors with the same molecule we use to attack them lets us know exactly where the treatment will go and helps us determine if a given radioisotope therapy will be effective for an individual patient,” says Thor Halfdanarson, M.D., an oncologist who specializes in treating neuroendocrine and pancreatic cancers. “It’s not often in cancer care that we’re able to see the target before we send in the treatment.”

Radiopharmaceutical therapy can be beneficial for patients with advanced cancers whose tumors aren’t responding to or can’t be readily addressed by other traditional treatment options. It is also comparatively gentle, according to Dr. Johnson.

“The therapies already on the market have been very effective. They’re not perfect, but they have low toxicity, and in my experience, patients have loved them,” he says. “It’s a very rewarding field, because we love to see patients happy with their care.”

This type of technology isn’t new. It has its origins in the use of radioactive iodine to treat thyroid cancer. In recent years, researchers and clinicians have been developing new theranostic technologies for better imaging and cancer treatment. There are now several Food and Drug Administration-approved radiopharmaceuticals available for treating neuroendocrine and prostate cancer tumors, but the field remains ripe for identifying new cancer targets and new radioisotopes.

Leading the Field

This investment can be seen not only in the new clinical expertise on campus but also in new facilities and partnerships. Mayo Clinic is building new tools and collaborating with industry partners to develop the next generation of theranostic imaging and radioisotope technologies, as well as addressing access issues for patients.

These collaborations lay the foundation for the testing and application of new theranostic treatments for patients with cancer, something that Mayo Clinic continues to put front and center in its practice. One major recent advance is the licensing of a Mayo-developed technology, called PSMA Alpha-PET DoubLET, to Perspective Therapeutics.

“Alpha-emitting radioisotopes have so much more potential to be powerful, and targeted, but they come with a long list of challenges,” says Dr. Johnson. “One of the biggest challenges is that we can’t easily see exactly where they go in the body. The technology we’ve developed really flips the script. We’ve taken what was the main issue with alpha-emitters and made it even better than what we see with beta-emitters.”

The technology uses a targeting molecule that binds to a chemical found on the surface of prostate cancer cells called prostate-specific membrane antigen (PSMA). The unique design allows these targeting molecules to carry either copper-64, which can be used to image the prostate cancer cells on a PET scanner, or lead-212, which releases alpha particles to treat the cancer. This allows researchers to use the same base molecular structure for both radioisotopes, which is not otherwise an option.

Dr. Johnson and a team of researchers at Mayo Clinic devised the idea and technology behind PSMA Alpha-PET DoubLET in the lab and ran it through promising preclinical testing before the technology was licensed to Perspective Therapeutics. The company is now further developing the platform to test in human clinical trials.

Progress also has been made on identifying and testing new and better cellular targets for radioisotopes. The team at Mayo Clinic is currently investigating a new targeting molecule for multiple cancers, called fibroblast activation protein inhibitor (FAPI). This molecule has already been used to successfully image pancreatic cancer tumors. Now researchers are investigating its use for delivering alpha-emitting radiation therapy to these notoriously hard-to-target tumors.

Teams at Mayo Clinic also are supporting a multitude of clinical trials in the theranostic space, including applying alpha-emitting radioisotopes to treat melanoma and next-generation beta-emitters for treating prostate cancer. Some clinical trials are investigating whether theranostic approaches may be beneficial even in earlier cancer stages before other types of treatment are implemented. In the lab, researchers are working to understand who the best candidates for radiopharma-ceutical treatments might be and developing new molecules that are longer lasting, are better at targeting cancer and have fewer side effects.

“This has always been a dream of mine,” says Dr. Johnson. “With my research background, I’m working as a clinician, but I also want to see what’s going on in the clinic, take it to the lab, design something new and bring it back to clinical trials so that we can get it to the patients. Doing that whole loop — it’s something that’s on my bucket list, and we might just pull it off.”

While many of these studies and trials are still in their earliest phases, the team is already looking toward a bright future for theranostics.

“Right now we’re in the ‘blue sky’ period,” says Dr. Sartor. “We have a limited number of successful therapies already available to patients, but now that we’ve demonstrated the proof of principle, we know that if we can get the radioisotope to the right spot, we can kill the tumor. We’re in a mad rush to identify new targets, carriers and efficient ways to engineer these treatments end to end.”