Theranostics, the pairing of a diagnostic imaging agent with a targeted radiopharmaceutical therapy, has moved from a niche corner of nuclear medicine into one of the most active areas of investment in oncology.
Major pharmaceutical companies, including Bristol Myers Squibb, Johnson & Johnson and Eli Lilly, are running development programs. Experts project that within 15 years, 60% of radiation delivered to treat cancer will come from radiopharmaceuticals, compared to roughly 2% today.
At the University of Kentucky Markey Cancer Center, radiation oncologist Denise Fabian, MD, is building the center’s radiopharmaceutical therapy program and is an active voice in the field nationally, having chaired a CME symposium on theranostics for NRG Oncology earlier this year.
Fabian recently spoke about where the field stands and what it takes to deliver these therapies well.
For oncologists who haven’t worked directly with radiopharmaceuticals, how does theranostics differ from other targeted therapies?
With other targeted therapies, you’re delivering a small molecule or an antibody that binds to a surface receptor and delivers a chemical payload. In theranostics, the payload is a radioactive isotope. That isotope decays and delivers radiation directly to the cancer cell.
What distinguishes theranostics specifically is the pairing of a diagnostic and a therapeutic agent that target the same molecule.
A patient undergoes an imaging scan first, and if the scan confirms the target receptor is present on the tumor, they’re a candidate for the matched therapy. The diagnostic and the therapeutic are linked from the start—that’s the concept the field is built on.
The particles themselves may also differ from what we use in external beam radiation. For example, you can deliver alpha particles, which are highly potent and cause substantial DNA damage, or beta particles, depending on the isotope.
What makes the field so active right now is the ability to mix and match.
The field now has improved chelators, ligands, and higher-affinity peptides and antibodies. You can pair different radioactive isotopes with different homing molecules, and if you can identify a receptor target on the tumor, you can theoretically get a radiopharmaceutical to that target.
The number of possible combinations is very large, and that’s one of the reasons you’re seeing so much investment.
What cancer types currently have approved theranostic agents?
Thyroid cancer has been treated with radioactive iodine for decades, making it the original and most successful theranostic agent.
Prostate cancer has two approved agents: Xofigo (radium-223) for patients with castration-resistant prostate cancer with symptomatic bone metastases, and Pluvicto (lutetium-177 vipivotide tetraxetan) for PSMA-positive metastatic castration-resistant prostate cancer.
Neuroendocrine tumors can be treated with Lutathera (lutetium-177 DOTATATE), which targets the somatostatin receptor. Those are the most established indications, and many others are being studied in clinical trials.
Markey has 13 active radiopharmaceutical trials. Can you describe the scope of that work?
Many of the studies are phase I dose escalation trials, establishing the appropriate dose without limiting toxicities. Efficacy trials follow from there.
We’re looking at several receptor targets, including gastrin-releasing peptide receptor (GRPR) and fibroblast activation protein (FAP). These involve linking a targeting molecule to a therapeutic isotope like lead-212 or lutetium-177 and delivering that directly to the tumor.
I’m also developing a cervical cancer trial through NRG Oncology that, if approved, would be one of the first theranostics trials to advance through that cooperative group.
What does it take for a cancer program to deliver these therapies?
It’s substantial, and I think programs sometimes look at the list of requirements and feel overwhelmed. But it’s worth remembering that radioactive iodine has been delivered safely for decades in outpatient settings. The infrastructure for that exists broadly.
For newer radiopharmaceuticals, you need regulatory licensure, a strong radiation safety program, appropriate equipment (SPECT scanners, dose calibrators, special delivery rooms) and the right personnel, such as a nuclear pharmacist and trained technicians.
Logistically, these agents are also time-sensitive in a way that most drugs aren’t. They are actively decaying from the moment they’re manufactured, so are produced to be delivered on a specific day and time. Some companies charter flights to get agents to treatment sites on schedule.
The other piece, and I think the most important one, is the multidisciplinary team. Nuclear medicine, medical oncology, and radiation oncology all have a stake in this space. To identify the right patients, select the right agents and manage delivery safely, you need expertise from all three.
Where do you see the field going over the next several years?
The pipeline is very robust right now, with many agents currently in a lot of dose-escalation and early phase studies. The emergence of efficacy data will determine whether these agents outperform current standard of care across more disease sites, and I expect approvals to follow in cancers beyond the current approved indications.
What I think is underappreciated is how much the patient selection piece is going to evolve. The ability to use an imaging agent to screen patients before committing to therapy is a meaningful shift.
You’re not waiting for a tissue biopsy result or relying solely on what a tumor looks like under a microscope. With theranostics, you can visualize in real time whether the target is present.
As more elementally matched imaging-therapy pairs are developed, patient selection will become more precise, and that should improve outcomes.
The multidisciplinary piece is also going to matter more. As the number of available agents grows, no single specialty will be able to manage this alone. Programs that have built real collaboration between nuclear medicine, medical oncology and radiation oncology will be better positioned to move patients through appropriately.
The field is moving fast, and the infrastructure and the teamwork need to keep pace.
