Role of FDG-PET Vs FES-PET in ER+ Breast Cancer

Gary Ulaner, MD, PhD: It’s important to clarify that FES–PET [positron emission tomography] is different from what we consider PET imaging. PET is mostly FDG [fluorodeoxyglucose]–PET. FDG is a glucose molecule, so the FDG-PET scan allows us to evaluate metabolism. Because cancer cells are often very metabolically active, we can use FDG-PET to detect cancer cells. FES-PET is an entirely distinct examination. It uses the same scanner, a PET scanner, but the agent that’s administered to the patients is entirely different. It is this fluorinated estrogen that finds the estrogen receptor [ER].

Lesions on FES-PET show us estrogen receptor. It’s not going to find estrogen receptor–negative breast cancer. It’s not going to find other types of cancers that are estrogen negative. It’s going to specifically allow us to visualize estrogen receptor–positive breast cancers, whereas FDG allows us to see metabolism. Keeping this in mind, there’s going to be a growing number of these agents that we’re using with PET scans. It’s going to be important to identify what type of PET scan we’re performing. When someone says, “We should order a PET scan,” it’s going to be important to know, “Do you want an FDG-PET scan to evaluate metabolism? Do you want a FES-PET scan to evaluate the estrogen receptor? Do you want some of the other types of PET scans that are being developed?”

Let’s talk a little more about the FES-PET scan, what it can do, and then what are some of the potential applications in patients with estrogen receptor–positive breast cancer. Importantly, this FES molecule that finds estrogen receptor can demonstrate metastases that we can’t see on anatomic imaging like CT [computed tomography] scans. On this slide, on the left slide, you see an image of the whole-body FES-PET scan, known as a MIP image, a maximum intensity projection image.

The image on the right is an axial image from a CT scan, which is anatomic imaging. It has an overlay of both, so you’re looking at the CT scan overlaid with the information that you’re getting from the FES-PET scan. It’s important. As you can see on the right image, there’s a lesion in a bone on the CT scan, which we don’t see on the FES-PET scan. There’s also a focus on the FES-PET overlay with no correlative anatomic finding on the CT scan. These images provide different information, and we have to bring them together to accurately determine the diagnosis in an individual case. For the lesion on the CT scan—what we’ve seen on the CT scan is a sclerotic lesion, but we don’t see it on the FES-PET scan because this is a patient with ER+ breast cancer. This is probably an old treated lesion, where there was a metastasis previously, but there’s no active estrogen receptor in the lesion. This is a treated site of disease. But the focus on the FES-PET scan demonstrates an active site of estrogen receptor–positive tumor, even though you can’t see it on the CT scan.

Another important issue to raise in comparing the FES-PET scan with the more common FDG-PET scan is that these 2 scans can work cooperatively to demonstrate heterogeneity of individual lesions in a single patient. We can see some lesions, such as the images on the left, on the FES-PET scan that are showing estrogen receptor. They aren’t seen on the images on the right, which are the FDG-PET images of metabolism. These are sites of malignancy that happen to express a lot of available estrogen receptor but are not metabolically active.

There are also lesions seen on the FDG-PET scan that aren’t seen on the FES-PET scan. These are sites of disease as well. But these sites of disease are much more metabolically active and maybe more aggressive, whereas the estrogen receptor is either not available for us to visualize or not present at all. These are breast cancer metastases, but there are different types of breast cancer metastases being visualized by the different imaging agents. Some are very FES-avid, very estrogen receptor–positive, and not very metabolically active. Others are very metabolically active and potentially more aggressive, but these do not show estrogen receptor availability.

I want to take a moment to note that, because this is a molecular imaging agent that finds the estrogen receptor, patients using drugs that affect the estrogen receptor will need to be withdrawn and paused before a FES-PET scan will give valid results. Patients on tamoxifen or fulvestrant may need to pause use of those agents prior to 1 FES-PET scan to be accurate. This is what a FES-PET scan looks like on imaging. The agent is excreted in the liver, into the biliary tree and the bowel, so we’ll often see the liver and the bowel as either what are called hot spots or, in a black-and-white image, very black.

The agent is also excreted to a lesser extent through the kidney into the ureter and the bladder, so we may see those organs as well. The agent is extensively excreted through the liver, so it may be hard to visualize lesions in the lever, particularly on a standard, what we call PET window. On the left, this is a PET window going from 0 to 10 SUV [standardized uptake value] units. If you expand the PET window, the image on the right is from 0 to 30 SUV. Now you might begin to see through the liver and may be able to find lesions in a way that you can’t on the standard window.

Transcript Edited for Clarity