Targeting PSMA in Prostate Cancer Treatment - Episode 2

Defining PSMA-PET Scans for Prostate Cancer

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Phillip J. Koo, MD, provides a detailed explanation of the process of PSMA-PET imaging scans for prostate cancer.

Alicia Morgans, MD, MPH: One thing that’s important is that we understand what a PSMA [prostate-specific membrane antigen] PET [positron emission tomography] scan does, how it works, and how it can be useful in our practice. Phil, can you go through a little bit of the nuts and bolts of how PSMA PET scans work.

Phillip J. Koo, MD: PSMA stands for prostate-specific membrane antigen, and it’s a transmembrane protein on the surface of prostate cells. This is very different from what we’ve used in the past. Some people might be familiar with prostasin, which was more intercellular. But this is extracellular, and it works because it’s more specific to prostate cancer and upregulated significantly in patients with prostate cancer, which helps attract more of the radioisotope, allows for more of the positrons to be admitted, and allows for better imaging. It creates a bigger contrast between the target vs the background, which makes it easier to diagnose and read these images. In many ways, it’s become a perfect target for diagnosing disease, and because it’s more specific for prostate cancer cells, it lends itself to becoming a better therapeutic target as well.

If you look at the 2 major PSMA molecules approved in the United States, you have Gallium 68 PSMA-11 and fluorine F 18 DCFPyL. The major difference between these 2 agents is the isotope that creates the positron that allows for imaging. You have Gallium 68 vs F 18. Gallium 68 has roughly a 60-minute half-life, and F 18 has roughly a 2-hour half-life. If you look at the chemical structures, they’re pretty similar besides the radioactive isotope, besides the Gallium 68 vs the F 18. That small-molecule piece allows it to target the prostate-specific membrane antigen.

If you look at these images, you see a whole-body image from a DCFPyL patient, and you see the normal biodistribution that gives you the lay of the land. If you look underneath the bladder, you see some uptake that looks a little out of place. Then if you look at the cross-sectional images, you see the radiotracer localized to the prostate gland in this patient that has these brachytherapy seeds. Clearly, this patient likely has an elevated PSA [prostate-specific antigen] following brachytherapy that’s likely the source of the PSA. Then you go do the T2-weighted MRI, the actual images, and the diffusion-weighted images, and it corresponds. All these pieces of information together are telling you the story that this is where the PSA recurrence is originating.

Then you look at the story regarding FDA approvals of these PSMA-targeted diagnostic agents in the US. It was really groundbreaking in December of 2020 when we had the approval of Gallium 68 PSMA-11. It was a huge step forward; however, this approval was for UCLA [University of California, Los Angeles] and UCSF [University of California, San Francisco] because they submitted their own NDA [new drug application] for approval of this PET radioisotope, so access was limited then.

In May 2021, we had F 18 DCFPyL, which was commercialized by Lantheus and Progenics [Pharmaceuticals]. This opened the commercialization and the ability to distribute this across the United States. That was another landmark day. Then in December 2021, we had Gallium 68 PSMA-11, which is the same compound they used at UCLA and UCSF, but it was in a kit format. This kit format is what I like to call the shake-and-bake method of creating a radioisotope. It was approved, and now this can be distributed across the United States.

Alicia Morgans, MD, MPH: Thank you so much for that. As we think about different agents and how they can affect our staging and even be useful in more advanced disease, it’s rapidly evolving. Ulka, from your perspective, how is this imaging approach? How are these PSMA PET–targeted imaging compounds changing your practice?

Ulka Vaishampayan, MD: It’s changing our practice to risk profile patients much earlier. The way that seems to help is it allows us to avoid significant adverse effects from systemic therapies for prolonged periods of time. Honestly, if we can diagnose early on with very low PSAs, with the PSMA PET, we’re able to offer these patients salvage local therapies such as radiation or surgical resection, and render them in remission for a long time, delaying use of systemic therapy. The other side of it is in more advanced disease, it’s also helping us risk profile and treat patients earlier with treatment intensification to potentially change or alter their survival. The problem is that a lot of clinical trials haven’t incorporated this kind of imaging, and it will take us a while to prove if this early diagnosis is making a long-term survival impact.

Alicia Morgans, MD, MPH: Absolutely. We’re causing stage migration. We’re definitely changing management. Does that affect outcomes? As you said, that remains to be seen.

Transcript edited for clarity.