If you’re like most men, chances are you’re familiar with the initials PSA. They stand for prostate-specific antigen, a liquid protein produced by the prostate that serves as the basis for prostate cancer screening.
These days, you should also familiarize yourself with another abbreviation: PSMA, or prostate-specific membrane antigen. This protein is the target of specialized imaging technology that enables doctors to determine whether, and how extensively, prostate cancer has spread, or metastasized.
In this capacity, PSMA imaging can improve the ability to stage high-risk prostate cancer when it’s diagnosed or recurs after curative therapy. It also opened the door for targeted treatment of advanced cancers with a radiotherapeutic agent (see sidebar, “PSMA’s ‘Theranostic’ Capabilities”).
“PSMA provides a much more precise target to find where the cancer is and whether or not it’s still in the prostate or has extended outside the prostate,” says Andrei Purysko, MD, a Cleveland Clinic diagnostic radiology specialist. “This technology also unlocked the potential to not just perform the imaging diagnosis, but also to do the treatment for advanced prostate cancer.”
What Is PSMA?
The term prostate-specific membrane antigen is a bit of a misnomer because PSMA can be found on the surface of not only prostate cancer cells, but also to a lesser extent in cells elsewhere in the body.
Although its biological role in the body isn’t fully clear, PSMA is known to play a role in metabolizing dietary folate (vitamin B9) and glutamate, an amino acid that serves as a key chemical messenger (neurotransmitter) in the brain.
Why Is PSMA Important in Prostate Cancer?
What makes PSMA particularly valuable is that in the vast majority (90% or more) of cases, it is highly overexpressed in prostate cancer cells—as much as 100 to 1,000 times more than in other tissues, Dr. Purysko says. (Overexpression refers to the process in which a cell makes an abnormally higher number of specific proteins or biomarkers.)
What Is a PSMA-PET Scan?
This PSMA overexpression serves as the basis for the state-of-the-art positron emission tomography (PET) imaging that’s increasingly being used to detect advanced prostate cancer.
In the PSMA-PET scan, a specialist injects a radioactive tracing agent into a vein, usually in your arm. The tracer takes about an hour to distribute throughout your body and attach to PSMA-positive prostate cancer cells.
You’ll then undergo a PET scan, which captures images of your entire body. The radiotracer makes the prostate cancer cells “light up” on PET imaging, thereby showing the degree to which your prostate cancer has metastasized. PSMA-PET scans are usually combined with computed tomography in a PSMA-PET/CT scan, which provides a three-dimensional rendering of your internal structures.
“This is the fastest-growing imaging test that we have at Cleveland Clinic right now,” Dr. Purysko says. “It is the new standard of care for men with more aggressive disease.”
Who Should Consider a PSMA-PET Scan?
The scans can be used for men diagnosed with unfavorable- or high-risk prostate cancer, which is more likely to spread beyond the prostate and unlikely to be detected by conventional imaging, Dr. Purysko says. PSMA-PET imaging also is indicated for men who experience post-treatment PSA elevations, which may signal that prostate cancer has recurred.
Researchers are studying the PSMA-PET scan in other clinical scenarios. For instance, men with elevated PSA levels during prostate cancer screening typically undergo magnetic resonance imaging (MRI) to gauge their need for a prostate biopsy. In some cases, the MRI results are equivocal, making biopsy decisions less certain. PSMA-PET scans could help clear up this clinical picture. In the PRIMARY2 trial, researchers reported that among 660 men with nonsuspicious or equivocal MRI results but at high clinical risk for significant prostate cancer, use of PSMA-PET scans enabled 49% of participants to avoid a biopsy, without reducing diagnoses of clinically significant cancers (The Lancet Oncology, July 2026).
A PSMA-PET scan also may help detect small tumors in other areas of the prostate that MRI may miss. So, scientists are exploring its potential to help identify candidates for prostate cancer focal therapy, which targets only the cancer while sparing the rest of the prostate. Focal therapy has been shown to reduce the urinary and sexual side effects that accompany conventional whole-gland prostate cancer treatments.
Dr. Purysko cites the case of a friend diagnosed with prostate cancer who underwent dual MRI and PSMA-PET imaging, which confirmed his eligibility for focal therapy. After treatment, his PSA level dropped, and he’s shown no signs of cancer on biopsy since. “His erectile function has been completely normal since treatment, and he’s had no issues with incontinence,” Dr. Purysko says. “He’s doing just fine. It’s a very good success story, and when it’s a friend of yours, that’s an even better story.”
Understanding Your Results
At Cleveland Clinic, the results of PSMA-PET scans usually are ready within two days, but those times can vary at other sites, Dr. Purysko says.
If you’re deemed to be “PSMA positive,” that means your healthcare providers identified PSMA on the PET scan and may suggest additional testing to confirm the positive test finding. These results can then be used to determine your next course of action.
“The physician will inform the patient of the best options, depending on where the cancer is located,” Dr. Purysko says. “If there is disease outside the prostate, particularly outside of the pelvis, that generally means a patient needs an escalation of treatment with hormonal therapy, potentially with radiation therapy to the other sites.”
Risks and Limitations
In some men, PSMA-PET imaging may cause temporary side effects, such as headache, fatigue, nausea, mild allergic reactions, and a change in your sense of taste.
Although the PSMA-PET scan is effective at finding cancer, like any imaging study, it can miss a cancer. PSMA-PET scans also can produce false-positive results because certain benign conditions can cause accumulations (uptake) of the PSMA targeting agent. For example, nodules from benign prostate enlargement (BPH) and certain bone lesions—in particular, benign fibrous osseous lesions in the rib—can overexpress PSMA and be mistaken for cancer, Dr. Purysko says.
“The bone lesions have to be interpreted very carefully because not everything that shows PSMA uptake in the bone is going to be cancer,” he advises. “The test itself is elaborate, and the interpretation of the findings requires a lot of caution, expertise, and understanding where the false positives occur. So, it’s important that men look for centers with expertise and that they discuss the results with their physicians.”
Furthermore, due to their high sensitivity, PSMA-PET/CT scans can identify tiny micro-metastatic tumors that in the past might not otherwise have been detected with conventional testing and subsequently treated. It remains unclear whether treating these lesions alters the course of the disease, Dr. Purysko says.
“As a general principle, we believe that what we can see, we can address, but certainly, that doesn’t always translate into what we observe, we can address and improve outcomes. It’s going to take some time,” he says.
“At the end of the day, I think the net result is positive, despite some of the limitations and lack of data,” Dr. Purysko continues. “There are a number of patients who come with a treatment plan, and that plan can be changed quite significantly after the PSMA-PET scan. So, if it’s not offered in your initial visits when you’re talking to your physicians, you certainly should bring that up in your discussions.”
Not only do PSMA-PET scans help to diagnose and stage prostate cancer, but they also can be used to treat it—the term “theranostics” refers to the technology’s diagnostic and therapeutic capabilities, Dr. Purysko says. The scans guide treatment with lutetium Lu 177 vipivotide tetraxetan (Pluvicto), a form of precision radiation treatment combining the PSMA targeting agent with radioactive particles that attach to the PSMA-positive cancer cells.
“If you attach a stronger radioactive molecule to the same agent we use for imaging, that energy can be sufficient to destroy the cancer,” Dr. Purysko explains. “You’re placing the radioactive material mostly where the cancer is. It’s not a cure, but it certainly has been found to prolong survival.”
Pluvicto has gained regulatory approval for men with metastatic prostate cancer already treated with hormonal therapy and chemotherapy, as well as those who were treated with hormonal therapy and are considered to be appropriate to delay chemotherapy. And, in August 2026, it gained approval for use in combination with androgen receptor pathway inhibitors for men with metastatic prostate cancer who still respond to hormonal treatments, meaning it can be used earlier in the disease process to reduce the risk of progression or death. Note that you must have good PSMA overexpression (as shown on the PSMA-PET scan) to be a candidate for treatment, Dr. Purysko advises.
Pluvicto can have toxic effects on the kidneys and bone marrow, and patients can experience severe dry mouth and dry eye, Dr. Purysko says. Discuss these potential risks with your physician.
