The Promise Of Radioligand Therapy For Advanced Prostate Cancer

“You have to think of [Pluvicto] as having two arms. One arm recognizes PSMA, which is a protein expressed on the prostate cancer, and the other arm has radiation therapy attached to it,” Dr. Sumit Subudhi, a medical oncologist at University of Texas MD Anderson Cancer Center in Houston, tells SurvivorNet.

“Think of it as a heat seeking missile that actually finds the PSMA expressed in prostate cancer and delivers the radiation right there.”

What Is Radioligand Therapy?

Radioligand therapy is somewhat similar to a guided missile, designed to seek out a very specific target and deliver its payload with incredible accuracy, leaving everything else untouched. It’s a cutting-edge cancer treatment that truly merges two powerful concepts: the precise targeting ability of drug therapy and the cell-killing power of radiation.

In simple terms, this innovative approach uses a special molecule, called a “ligand,” that’s designed to specifically find and attach to cancer cells. This ligand is then chemically linked to a tiny bit of radioactive material, forming what’s called a “radioligand.”

Once injected into your bloodstream, this radioligand travels throughout your body, seeking out those specific cancer cells. When it latches onto them, it delivers a localized, powerful dose of radiation directly to the tumor site. This remarkable precision helps to limit damage to the surrounding healthy tissues, which is a major advantage compared to more generalized treatments like traditional chemotherapy or external radiation that can affect a broader area of the body.

This type of therapy is often referred to as a “theranostic” approach because it combines both “therapy” (treatment) and “diagnostic” (detection) capabilities in a personalized way.

Pluvicto: A Targeted Strike

One of the most significant advancements in radioligand therapy for prostate cancer is a drug called Pluvicto (also known as lutetium Lu 177 vipivotide tetraxetan).

The secret to Pluvicto’s precision lies in a protein called prostate-specific membrane antigen (PSMA). PSMA is commonly found on the surface of prostate cancer cells. While normal prostate cells have some PSMA, prostate cancer cells, particularly those in advanced or aggressive stages, have a significantly higher concentration of it. This makes PSMA a valuable “lock” for Pluvicto’s “key.”

When Pluvicto is injected, its ligand component binds tightly to the PSMA on the cancer cells. Once attached, the radioactive part, lutetium-177, emits a type of radiation called beta radiation over a very short distance, typically just a few millimeters. This localized radiation damages the DNA of the nearby cancer cells, ultimately causing them to die. The beauty of this “proximity effect” is that healthy tissues, which either don’t express PSMA or express very little of it, are exposed to far less radiation than the cancer cells themselves. This significantly minimizes harm to your healthy organs and tissues.

Because Pluvicto circulates throughout your body, it can treat cancer in multiple locations at once, including the main tumor and any metastases (cancerous lesions that have spread to other parts of the body). This systemic reach is crucial for advanced disease.

Is Pluvicto Right For You?

Pluvicto is not a treatment for all patients with prostate cancer, Dr. Subudhi explains. It is specifically approved for men with metastatic castration-resistant prostate cancer (mCRPC). This means your prostate cancer has spread beyond the prostate and is no longer responding to traditional hormone therapy (also known as androgen deprivation therapy or ADT).

“At this time, the only people getting radioligands are those with metastatic castration resistant prostate cancer, and most of these patients have failed an ARPI [another form of hormone therapy], such as abiraterone, apalutamide, darolutamide or enzalutamide. These patients have a choice of getting chemotherapy [or] a radioligand therapy,” Dr. Subudhi says.

Historically, Pluvicto was only available for patients who had already undergone chemotherapy. However, in March 2025, the FDA expanded its approval. Pluvicto is now available to a broader group of patients: adults with PSMA-positive mCRPC who have been treated with an androgen receptor pathway inhibitor (ARPI) (like abiraterone or enzalutamide) and are considered appropriate to delay taxane-based chemotherapy.

This expansion is a major step forward, as it can triple the number of eligible patients, offering more men access to this innovative therapy earlier in their treatment journey.

To be eligible for Pluvicto, patients generally must meet these key criteria:

• Confirmed mCRPC: Your cancer has spread and is no longer responding to hormone therapy.
• Progressed after at least one androgen receptor pathway inhibitor (ARPI): You’ve already received a hormone-based treatment, and your disease has continued to progress.
• Evidence of PSMA-positive disease: This is crucial. Your cancer cells must express the PSMA protein, which is confirmed through a specialized imaging test.

It’s important to clarify that Pluvicto is not intended for newly diagnosed localized prostate cancer. It does not currently have a role as an alternative to definitive therapy like surgery or traditional radiation for localized disease.

Pluvicto is also a preferred option over other bone-targeted radioisotopes like Radium-223 (Ra-223, brand name Xofigo) for PSMA-positive disease. While Xofigo is used for symptomatic bone-only metastases, Pluvicto has a more favorable side effect profile and is less likely to cause significant bone marrow failure, which could limit future treatment options like chemotherapy.

The Critical Role Of The 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.

Here’s why the PSMA PET scan is so important:

• Confirmation of PSMA Expression: 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.
• “Lighting Up” Cancer Cells: Areas that “light up” on the scan indicate PSMA-positive disease. This helps your medical team determine if Pluvicto is likely to be effective for you.
• Guiding Treatment Decisions: The degree or amount of that PSMA expression does seem to have some correlation with how well Pluvicto may work. If you have a high level of PSMA expression, you are more likely to respond well to Pluvicto.
• Finding Hidden Tumors: 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. This is why the PSMA PET scan is a critical step in deciding if Pluvicto is the right path for you.

What To Expect During Your Pluvicto Treatment

Pluvicto is typically administered once every six weeks, for up to six treatment cycles. Each treatment is given through an intravenous (IV) infusion in a clinic or hospital setting, and the entire process usually takes a few hours from start to finish. You generally won’t need to fast or do any special preparations beforehand.

Throughout your treatment, your medical team will closely monitor your progress and health. Before each cycle, you may undergo lab tests and imaging to see how the cancer is responding and to check for any potential side effects or toxicity, especially to your bone marrow and kidneys. If you’re responding well and tolerating the treatment, it will continue.

Other Radioisotopes

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 mimics calcium. And as we know, we take calcium supplements because it helps our bone,” Dr. Subudhi explains.

Radium-223 is a radioactive drug that is actually taken up by the cells that form new bone, he explains. These cells are more active in areas where prostate cancer has moved into the bone, and as they take up the Radium-223, it emits radiation that locally kills the cancer.

In summary, Xofigo is a form of radiation that is given through an IV and selectively targets cancer that has spread to bones. Studies have shown that it can improve overall survival and reduce symptomatic skeletal related events (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.

Side Effects Of Radioligand Therapy

Like any cancer treatment, Pluvicto can cause side effects. Your medical team will monitor you closely and help you manage any side effects you experience.

Some of these side effects are related to the way the radioactive compound behaves in the body. Some normal parts of your body also express PSMA (places like the salivary gland or the liver) and so, the side effects that we see typically come from getting radioactivity to places in the body where we don’t intend it.

These might include:

• Fatigue (feeling tired or lacking energy)
• Nausea or vomiting
• Dry mouth (due to the salivary glands taking up some radiation)
• Loss of appetite
• Decreased blood counts, such as anemia (low red blood cells), low white blood cells, or low platelets

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.

Questions To Ask Your Doctor

• Am I eligible for radioligand therapy, specifically Pluvicto?
• Have I had, or can I undergo, a PSMA PET scan to determine if my cancer is PSMA-positive?
• How often will I be monitored while undergoing this therapy, including lab tests and imaging?
• What side effects should I expect, and what steps can I take to manage them?
• How does Pluvicto compare to other treatment options available for my specific situation?

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

 

Learn more about SurvivorNet's rigorous medical review process.

---