Radioligand Therapy: Who Is Eligible & How Does It Work?

“Radiopharmaceuticals are a newer category of medication,” Dr. Edward Yen, a clinical medical oncologist at Baylor College of Medicine in Houston, tells SurvivorNet. “They’ve actually been around for some time, but because of the advances in that kind of technology and option, I think a lot of the medications have made big splashes in clinical trials recently … And it’s probably going to shape the way that prostate cancer is going to be treated over the next decade.”

What Is Radioligand Therapy?

Imagine a treatment that can find cancer cells wherever they are in your body and deliver a precise, powerful strike directly to them, while largely sparing healthy tissues. That’s the essence of radioligand therapy. It’s a cutting-edge approach that brings together two powerful concepts in cancer care: the targeting accuracy of a specific drug and the cell-killing ability of radiation.

Here’s a breakdown of how it works:

• The Ligand: Scientists design a special molecule, called a “ligand,” that has a unique ability to seek out and attach to certain proteins found mostly on the surface of cancer cells. For prostate cancer, this target protein is called Prostate-Specific Membrane Antigen, or PSMA.
• The Radioactive Isotope: This molecule is then chemically linked to a tiny amount of a radioactive substance, or “isotope.” Together, they form what’s called a “radioligand”.
• Targeted Delivery: Once this radioligand is injected into your bloodstream, it travels throughout your body. Because the ligand is specifically designed to bind to PSMA, it largely bypasses healthy cells and targets the cancer cells that express this protein.
• Precise Radiation Delivery: When the radioligand latches onto the cancer cell, the attached radioactive isotope releases a small, localized dose of radiation. This radiation damages the DNA of the nearby cancer cells, ultimately causing them to die.

“Before we were utilizing earlier versions of radiopharmaceuticals, mainly for palliation, so specifically to just address symptoms like pain,” Dr. Yen explains.

“However, starting maybe not quite 10 years ago, there was a medication called Xofigo, and that one not only helped with bone pain, but it also caused a survival benefit in patients who were treated with it. And so that was a really exciting moment. And more recently, there was a medication, a radiopharmaceutical, called Pluvicto … ultimately, it’s been shown to have a survival benefit,” he adds.

Pluvicto: A Targeted Radioligand Therapy

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) has been approved by the FDA for treating certain types of advanced prostate cancer. It consists of two key parts: a ligand designed to target PSMA, and a radioactive isotope called lutetium-177.

For prostate cancer cases, Pluvicto utilizes the fact that most prostate cancer cells express PSMA. While normal prostate cells have some PSMA, prostate cancer cells — especially those in advanced or aggressive stages — have a significantly higher concentration of it. This makes PSMA an excellent target.

When Pluvicto is injected, it travels through your bloodstream, seeks out these PSMA-expressing cancer cells, binds to them, and delivers a localized dose of radiation. This systemic delivery means it can treat not only the main tumor but also any cancerous lesions that have spread throughout the body, known as metastases.

Who Is Eligible For Pluvicto?

It’s very important to understand that Pluvicto is not for all patients with prostate cancer. Oncologists emphasize that it does not have a role in newly diagnosed localized prostate cancer. For localized disease, standard therapies like surgery or traditional radiation with curative intent are still the primary approach.

Pluvicto is specifically approved for men with metastatic castration-resistant prostate cancer (mCRPC). This means your prostate cancer:

• Has spread beyond the prostate to other parts of your body
• No longer responds to traditional hormone therapy

In a significant advancement, the FDA expanded the use of Pluvicto on March 28, 2025. Previously, it was only available for patients who had already undergone chemotherapy. Now, it can be used earlier in the treatment journey, specifically for adults with PSMA-positive mCRPC who have been treated with an androgen receptor pathway inhibitor (ARPI) and are considered appropriate to delay taxane-based chemotherapy.

This expansion is a major step forward, potentially tripling the number of eligible patients.

To be eligible for Pluvicto, patients generally must have:

• Confirmed mCRPC
• Progressed after at least one androgen receptor pathway inhibitor (like abiraterone or enzalutamide)
• Evidence of PSMA-positive disease, which must be confirmed via a specialized imaging test

The Critical Role Of A PSMA PET Scan

This brings us to a crucial step in determining eligibility: the PSMA PET scan. This is a specialized imaging test that can detect prostate cancer cells based on how much PSMA protein they express.

Before you can receive Pluvicto, your doctors need to be sure that your cancer cells actually express PSMA. During this scan, a small amount of a radioactive tracer that binds to PSMA is injected into your body. Areas that “light up” on the scan indicate PSMA-positive disease. This helps your medical team determine if you are eligible for Pluvicto.

If you have a high level of PSMA expression, you are more likely to respond well to Pluvicto.

PSMA PET scan can also find small spots of tumor much earlier than older imaging methods.

If your cancer has PSMA-negative or low-expressing tumors, the radioligand may not bind effectively, and the treatment may be less beneficial.

What To Expect During Treatment

Once eligibility is confirmed, the treatment process is carefully managed. Pluvicto is typically administered through an intravenous (IV) infusion in a clinic or hospital setting. Each treatment session usually takes a few hours from start to finish.

The therapy is generally given once every six weeks, for a total of up to six treatment cycles. Before each treatment cycle, your medical team will likely perform lab tests and imaging to monitor how your cancer is responding and to check for any potential side effects or toxicity, especially to your bone marrow and kidneys. You typically don’t need to fast or prepare in any other special way before receiving the infusion.

Potential Side Effects

Like any cancer treatment, Pluvicto can cause side effects.

“Side effects of Pluvicto, in general, depend on the radiation and where the medication goes,” Dr. Yen explains.

“Radiation potentially can cause your blood counts to come down, so we’ll usually have to watch that very carefully. It can also go to other areas of your body, where PSMA is expressed, and these would be considered off-target effects,” he adds. “One common one is that it can go to your salivary glands, and that can, in turn, cause dry mouth. So we watch that very carefully, but in general, compared to other medications, this medication is pretty well-tolerated.”

Common side effects of Pluvicto include:

• Fatigue
• Nausea or vomiting
• Dry mouth (xerostomia)
• Loss of appetite
• Mild bone marrow suppression

Rare but more serious side effects may include kidney issues, especially if you have pre-existing kidney disease, or more severe bone marrow suppression. This is why close monitoring with blood tests before each dose is so important. Overall, however, Pluvicto has generally been well-tolerated by patients.

Pluvicto vs. Other Radioisotopes (Radium-223)

You might also hear about other types of radioisotope therapies for prostate cancer, such as Radium-223 (Ra-223, brand name Xofigo).

Radium-223 is another option for men with symptomatic mCRPC who have bone metastases only (no evidence of spread to internal organs like the liver or large lymph nodes).

Xofigo is a form of radiation that is given through an IV and selectively targets cancer that has spread to bones. Studies have shown to improve overall survival and reduce symptomatic SREs compared to best supportive care.

While effective, Xofigo can sometimes permanently reduce your bone marrow reserves, which might limit your ability to receive certain cytotoxic chemotherapies in the future. Due to this concern and the benefits of Pluvicto, Pluvicto has largely replaced Xofigo in areas where it is available.

The Benefits of Pluvicto

For eligible patients, Pluvicto offers several significant potential benefits that can dramatically impact your quality of life and prognosis including delay in disease progression, symptom relief, and improved survival.

Clinical trials have shown that Pluvicto can extend overall survival in patients with advanced, treatment-resistant prostate cancer. One Phase III trial demonstrated that 177Lu-PSMA-617 improved median overall survival from 11.3 to 15.3 months.

Compared to traditional chemotherapy, radioligand therapy causes less damage to healthy tissues, which can result in fewer severe side effects. Because it circulates throughout the body, Pluvicto can treat cancer in multiple locations at once, including hard-to-reach metastases. This means it can find and target cancer cells that might not be visible or treatable with localized methods.

While it’s important to understand that Pluvicto is not a cure, it offers a meaningful and promising option for patients who might otherwise have very limited therapeutic choices. It also notably does not impair the ability to receive chemotherapy later if needed.

Questions To Ask Your Doctor

• Am I eligible for radioligand therapy like Pluvicto?
• Have I undergone, or can I undergo, a PSMA PET scan?
• What are the benefits and potential risks of this treatment for my individual case?
• What side effects should I expect, and what steps can I take to manage them?
• How often will I be monitored while undergoing this therapy?

Content independently created by SurvivorNet with support from Novartis Pharmaceuticals Corp.

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