Ephraim Parent: Hello and welcome. Today, we are here to have a series of lectures about molecular imaging of prostate cancer. My name is Ephraim Parent, I'm a radiologist at Mayo Clinic, and the lecture today will be on the bone imaging aspect of prostate cancer.

This short lecture will cover a few topics. Principally, the role of bone imaging, or skeletal imaging, in prostate cancer, and cover the common ways we do planar, and then more advanced 3D imaging, and how this applies to how your physician will be using this information to treat and manage your prostate cancer.

So to start off with, we're going to talk about the goals of imaging, and these are pretty much only two things. Why do we do this? One, we want to identify if there is, in fact, any evidence of metastatic prostate cancer to the skeleton, and how much of it there is. And then the second part is related to that, but it involves subsequent therapies. There are subsequent images to where we can evaluate the effectiveness of the therapy that your physician might've placed you on.

Why do we get a bone scan? Bone is often the primary site, or may also be the only site, of metastatic disease in patients with prostate cancer. The bone scintigraphy, or this kind of planar imaging, provides a total skeletal survey, which has relatively low cost, and it has high sensitivity and is a fairly easy and reproducible study that is commonly used for most patients that have prostate cancer, and especially if they have suspicion for metastatic disease.

There are two main radiopharmaceuticals, or molecular imaging agents, which we use in nuclear medicine to identify for osseous metastatic disease. The first one is technetium-99m, MDP, or methylene diphosphonate. And the other one is a very similar agent that works very similarly, but it's a different type of technology, what we use, it's called sodium chloride, and that's a PET study. We'll be talking about both of these, but these are the most, very commonly used, as a marker of bone metastatic disease.

This is a planar image, on the right, of a patient with prostate cancer. There's not really anything here that would suggest this person has prostate cancer, metastatic disease, in the skeleton at least. This is a relatively normal-looking study. I have highlighted an area that I'm pointing to with the red arrow that has, but you see on these anterior and posterior images, and that's where the site was injected. But that dot, if it was other places in the skeleton, that would be very typical of what we would see with somebody with prostate cancer, where we have areas of uptake correspond to increased blood flow and other things that we see with prostate cancer. It's a very good marker for disease.

This has two patients that we have seen with prostate cancer, different types of patterns that we see. The first patient, on the left, has what we call oligometastatic osseous disease; meaning that there are several areas, but it's not extensive throughout. I've identified a few areas here, such as along the right clavicle and the spine, where you see an increased uptick of this tracer, and those are areas that we would expect to see prostate cancer.

The other patient on the right, we don't really see any focal lesions, but what we see is, there's this nodular appearance throughout the skeleton. And in fact, this patient has what we refer to, colloquially, as a super scan, where there's so much activity through, and so much disease through the skeleton, that things become confluent, and we say there's this extensive disease where you're no longer able to identify individual lesions. But these are both clinical presentations that we see often.

To evaluate how we identify the effectiveness of treatment, we can take serial time points, and understand how the disease in the skeleton is either getting worse or better over time. These are three images of the same patient over different time points in the course of therapy. On the image on the left, we have a few areas of increased uptake, suggestive of osseous metastatic disease involving the right humeral head, skeleton, and several ribs. And underneath that, I've indicated the patient's PSA, which is often a marker, a lab marker, that we can use to identify how much disease is circulating in the body.

The next image, the center image, is where we see that the PSA has gone up, but he now also has extensive disease, including those same areas but now, throughout the spine, multiple ribs have this nodular appearance which implies that there's much disease through them. And also increasing uptake in that right humeral head.

Therapy was changed, and on the last image, we see at this time point, the PSA has gone down, as well as much of the disease in the spine and ribs have gone down, but that right humeral head actually has increased uptake.

All of these findings are suggestive that while he's overall responding favorably to disease, there is a mixed pattern of uptake, suggests that there are perhaps some areas of worsening disease. The point of this is to show that we get a sense of these things changing over time, which can help the treating physician know how best to treat and maintain management for the patient.

Now, what I've been showing you is, it's more of a visual assessment, but there are ways that we can get more accurate measurements that can be more precise as to the extent of disease, and again, how it's responding over time. This is where we take these planar images which we have been showing you, and turn them into a 3D image.

So on this patient that I'm showing here with both the anterior and posterior views, we see some uptake here on a rib, as well as some uptake in the pelvis. But what we want to be able to do with our 3D, or cross-sectional imaging, is to not just identify, but to quantify how much disease is in these sites.

And so the same patient, but now I'm showing you a sodium fluoride PET/CT, where we have uptake here on that hip. And you can see the sporadic lesion that I've indicated with arrows, and there is some uptake there.

And over time, we can take the same patient, this is the same patient that we were just seeing, and evaluate this uptake. We can get an actual number and compare that over time to see how the treatment is affecting. So where before, we had an SUV, which is a metric to evaluate how much radiotracer is going to this metastatic lesion. We can then also measure it again after therapy, and we see it's gone down, suggesting that the treatment that the patient's on is successful.

It's overall, these multiple time markers that we can use to be able to identify not only the extent of disease, but again, if the patient is responding favorably to treatment, and if there's a change in management needed.

Occasionally, we will use other types of molecular imaging, such as a fluciclovine, or PSMA study, that can help, in addition to the bone imaging, understand true disease. There is no one study that's perfect for everything, but we can often use both of these, the combination to identify whether or not there is a true disease.

For example, this patient on the left had a fluciclovine, or Axumin®, PET/CT, which is used also for prostate cancer. There is a lesion of uptake, or an area of uptake, in that left iliac bone. That's identified on both the cross-sectional and the coronal imaging there, as indicated by the arrow.

We did another study on sodium fluoride to evaluate whether or not this area was real, and there was no uptake in this area, suggesting that this was in fact, a false positive study. And it should be known that often it is multiple types of studies that are used to get a full and complete picture of the extent of metastatic disease in a patient.

So to conclude, typically planar bone scintigraphy is used to identify and manage prostate cancer. Occasionally, your physician, or the nuclear radiologist, will be using cross-sectional imaging to not only be more accurate in the extent of disease but able to truly quantify the extent of uptake and be able to provide tools to the treating physician to most appropriately manage therapy.

I'd like to thank the entire Prostate Cancer Working Group at the SNMMI for their help in putting these series together. Thank you.