Dr. Delphine Chen On Using PSMA PET Modalities to Detect Prostate Cancer

GU Oncology Now spoke to Delphine Chen, MD, Director of Molecular Imaging, Seattle Cancer Care Alliance, who spoke to us about the use of PSMA-Targeted PET imaging modalities for detecting prostate cancer.

GU Oncology Now: Can you start off by telling us about yourself, and your specialty?

Dr. Delphine Chen: Yeah. So I am a nuclear medicine physician. I focus on both diagnostic and therapy applications of nuclear medicine agents, which involve the use of radioactive drugs. It’s also called molecular imaging because our specialty focuses on imaging specific expression of different types of proteins or receptors, which distinguishes it from other imaging modalities like CAT scans or MRI scans. I’m the Director of Molecular Imaging at the Seattle Cancer Care Alliance and a Professor of Radiology at the University of Washington in Seattle.

Talk to us about the challenges of treating metastatic prostate cancer.

One of the main challenges is getting an accurate assessment of how extensive the prostate cancer is. That has been a common problem with all of the imaging modalities that we’ve had to date. We have very sensitive blood tests called PSA or prostate specific antigen blood tests that tell us when there is prostate cancer present but the imaging modalities we’ve used so far have been relatively insensitive.

So even though we can detect very small volumes of prostate cancer coming back, we may not be able to see those on imaging modalities and with metastatic prostate cancer, once we see them, then it’s a little easier to manage and we know we can characterize them by CAT scans or bone scans but when it’s, the challenge has been trying to detect when the metastases come back, after there has been treatment for what we believe is localized disease, meaning we believe we are treating with the intent to cure for localized disease. It’s all in the prostate, maybe local, metastases in the pelvis but usually we can get control of that disease. So trying to figure out when those metastases start coming and when to intervene has been a challenge.

What are the advantages of using PSMA-targeted PET imaging for advanced prostate cancer?

So PSMA PET is a very sensitive way of detecting prostate cancer. PSMA is in a protein that is expressed on the surface of prostate cancer cells and it’s expressed relatively specifically. So prostate cancers tend to have very high expression or high density of these receptors. And so when we inject a PSMA PET tracer or well, PET tracer that the PET tracer accumulates in high amounts where those prostate cancers are that express high levels of that PSMA. One of the challenges with PSMA PET is that not every prostate cancer expresses PSMA and PSMA stands for prostate specific membrane antigen. So that’s why it was first characterized as a specific marker of prostate cancers. So a few of the prostate cancers don’t take up that much PSMA on PET imaging because they don’t have the expression of the PSMA but the vast majority of prostate cancers that we have been trying to image with CAT scans and bone scans and MRI, most of those have expression of PSMA.

So that’s what makes PSMA PET such a great tool because we have a tracer that tells us specifically where this prostate cancer cells are and PET imaging in general is a highly sensitive modality. As long as we have a drug that accumulates in those prostate cancer cells at a high density, we can actually or I should say accumulates those cells in very high concentrations because there’s a high density of PSMA, we can often see very small metastases and that helps us find the sources of those rising PSA levels that we commonly see in prostate cancer patients when they start to recur and we have trouble finding where the cancer is. So that’s when PSA PET is really useful for trying to get at that, those earlier stages of when metastases are starting to develop.

How do you think PSMA-targeted PET imaging modalities will shape the future of prostate cancer care?

Well, I think we’re going to see, we’re going to have a better tool for characterizing the extent of prostate cancer. I think PSMA PET is going to be more and more utilized in a number of different settings for prostate cancer, not just in the setting I was talking about, which specifically is the patient who has had treatment for localized disease and now has a rising PSA level. And we’re trying to find where the recurrent prostate cancer is. We’re also using it for initial staging so can we better assess this extent of disease before we treat that localized prostate cancer to give us a higher likelihood of achieving cure after that initial treatment for the localized disease. We may also see it used more in the treatment monitoring setting, meaning, so a patient has metastatic prostate cancer already and we want to see if a treatment is working or not.

We may be able to see if the treatment is working earlier with the PSMA PET scan than with other modalities but that’s a hypothetical. We think that’s a possibility but that still remains to be investigated. There are a number of studies now coming out to show what are the effects of different therapies on the PSMA PET signal. Is that actually going to give us something about, information about how well the drug is working, how well the drug is engaging with its target? Those are open questions that we don’t know for sure yet if PSMA PET will be used in those contexts but in general, I think PSMA PET is going to be used more and more frequently in the care of prostate cancer patients because it does so well in characterizing the extent of disease.

Any closing thoughts?

No, I think this is an exciting time for nuclear medicine because of the new PSMA PET. The other future direction is PSMA therapies. The great thing about nuclear medicine is that because we use radioactive drugs, we can change that radioactive isotope that… Or I should say the radioactive label that we use for imaging, we can swap it out for a label that’s actually good for therapy. Since we know PSMA targets a number of prostate cancers really well, we can use the PSMA to deliver radiation specifically to those prostate cancer cells to kill them. That’s the next wave on the therapy side for nuclear medicine. So, yeah, it’s a really exciting time. We’re hoping that we can really improve treatment outcomes a lot for prostate cancer patients. I think a lot of prostate cancer patients are also really hopeful. We’re hoping to continue that trend in the field as we look at other agents to expand beyond the patients who don’t have that PSMA expression to try to give them the benefit of those same imaging and therapy tools.