Theranostics: A Powerful Diagnostic Tool and Cancer Treatment in One

A high-intensity radiation beam that penetrates the body to burn away tumors has been a standard weapon against cancer for more than a century.

Over the years, radiation therapy has improved dramatically, but its effectiveness against cancers in multiple places can be limited, and it can also destroy healthy tissues.

Now there’s a new weapon in the radiation therapy arsenal that can work better for cancers that have spread — and with fewer side effects, meaning a better quality of life for patients.

It’s called “theranostics,” because it combines therapy and diagnostics by using radioactive agents that first identify and then destroy individual cancer cells. After pioneering several developments in this field, MSK has new plans to expand the approach.

“We have a theranostic motto, which is ‘We see what we treat, and we treat what we see,’” says nuclear medicine physician Lisa Bodei, MD, PhD, Director of Targeted Radionuclide Therapy at MSK. “Regardless of disease, the concept stays the same — we detect the target with one radioactive substance and then treat it with a therapeutic one.”

How Theranostic Treatments Work Against Cancer

First, doctors infuse a patient with a radioactive drug — containing a diagnostic isotope — that binds to a specific target on cancer cells. Then, the patient gets a PET scan, a special type of imaging that “lights up” the isotope that has bonded to the cancerous cells.

Once the target cells are detected, doctors inject a treatment version of the imaging substance, which is loaded with a therapeutic isotope. At this point in the process, theranostics works like a smart bomb, zeroing in on the cancer cells and emitting radiation to kill them by destroying their DNA. The precision of theranostics means the healthy surrounding tissues are left unscathed.

Theranostics offers several advantages over more conventional treatments:

• Doctors can see the exact location of cancer cells that might be invisible on a conventional scan.
• Doctors can assess if a treatment is working more quickly.  
• Clinical trials can progress quickly from imaging phase to treatment phase.
• Treatment can be given to all sites of disease rather than just one at a time.

Even if theranostic treatments are not a cure, they can have a major impact in improving patients’ lives.

“It’s not just a matter of more effective therapies — it can sometimes be a better quality of life compared with standard therapies,” says Jason Lewis, PhD, Chief of the Radiochemistry and Imaging Sciences Service. “In many instances, theranostic treatments are very well tolerated, and patients can continue with their normal lives.”

Destroying Metastatic Prostate Cancer Cells With Theranostics

For Frank Shieh, theranostics stopped his metastatic (stage 4) prostate cancer in its tracks. Despite surgery, radiation, and hormone-blocking drugs after his diagnosis in 2010, the prostate cancer kept returning, eventually spreading to his bones. His PSA level, a marker for prostate cancer, was rising, suggesting the cancer was still progressing.

A physician himself, Dr. Shieh knew his situation was growing desperate. By 2022, his only option was to start chemotherapy, a daunting prospect for someone 83 years old.

He connected with MSK physician-scientist Yu Chen, MD, PhD, who proposed that Dr. Shieh join a clinical trial testing a theranostic treatment called ¹⁷⁷Lu-PSMA-617 (Pluvicto^®) for metastatic prostate cancer. Pluvicto targets a specific protein on the cancer cell surface called PSMA (prostate-specific membrane antigen) and destroys the cell.

“At that point, I was willing to try anything,” Dr. Shieh says. “The cancer had stayed in my body for so many years, and I was anxious to get rid of it.”

 

MSK’s Role in 177Lu-PSMA-617 FDA Approval as a Front-Line Prostate Cancer Treatment

MSK played a key role in developing this treatment, under the leadership of medical oncologist and Prostate Cancer Section Head Michael Morris, MD. His clinical trials led to approval by the U.S. Food and Drug Administration (FDA) to treat patients after chemotherapy had failed. In 2025, the approval was expanded to include patients like Dr. Shieh, who had never received chemotherapy — dramatically increasing the number of patients eligible to receive the treatment.

Theranostic Regimen With 177Lu-PSMA-617

Dr. Shieh received five injections of ¹⁷⁷Lu-PSMA-617 for five months. By the end of treatment, his PSA had dropped dramatically and has remained extremely low for two years.

“It’s been a relief to be able to go on with normal life without the cancer growing or having to deal with the effects of chemotherapy,” he says. “Being a doctor — and my wife is a nurse — we want to do what we can to make sure patients are aware these treatments are there to help them.”

How Theranostics Can Treat Other Cancers, Such as Neuroendocrine

MSK is identifying new theranostic targets in neuroendocrine cancers, which are aggressive and develop mainly in the prostate, lung, and gastrointestinal system. Dr. Bodei is leading a phase 1 trial that homes in on a target called a somatostatin receptor, found in neuroendocrine cancers in the gastrointestinal tract.

Targeting DLL3 Protein Cancers With Theranostics

Another new target is a protein called DLL3. Dr. Lewis and physician-scientist Charles M. Rudin, MD, PhD, developed an imaging agent that lights it up. Their 2024 paper in The Lancet Oncology showed that the agent reliably detected cancer cells containing DLL3. An accompanying commentary in the journal called the research “a pivotal milestone” for treating these cancers.

This is just the beginning, Dr. Bodei adds. “We are discovering additional targets and treatments for many other cancers, including breast cancer, brain tumors, kidney cancer, melanoma, and pancreatic cancer.”

Alpha Particles and the Next Wave of Treatment

MSK is positioned for the future of theranostics with a just-opened facility in Manhattan to test alpha-emitting radiopharmaceuticals — the most powerful form of theranostics yet.

These powerful agents can now be formulated on site at the new facility, streamlining their use in clinical trials.

“We’re the first academic institution in the U.S. with a laboratory dedicated to the clinical production of alpha-emitting radiopharmaceuticals,” Dr. Lewis says. “A lot of pharmaceutical and biotechnology companies are knocking down the door to work with MSK on new theranostic therapies.”

A New Era

To help the growing number of people with cancer, MSK is planning to expand the treatment space in the Manhattan campus and offer theranostic therapies at regional sites in New Jersey and New York state.

 

It will be a lifeline for more people like Dr. Shieh, who is so deeply grateful for the extra years he has been given with his wife and family, they’ve made a generous donation to support Dr. Chen’s continued research. Dr. Shieh enjoys playing piano, which relaxes and soothes his mind. He also plays a lot of golf and recently took up pickleball. They enjoy visiting their four daughters — two of whom are doctors themselves — and seven grandchildren.

“It’s wonderful that I’m able to be there for moments like my oldest grandson graduating from college this year,” he says. “As my wife says, I just need to keep this up until I’m 100 years old.”