My name is Gary Heller, and I'm here with Dr. Timothy Bateman, and our guest is Marcel DiCarli from Mass General Brigham Hospital and an expert on myocardial blood flow. So, we're interested in your perspectives of myocardial blood flow, which I think is incredibly important, and the new tracer of 15-floor period is. Well, thank you for having me here. I think this is such an important topic, and we have been discussing amongst ourselves and others that the quantification of flow is really the game-changer for nuclear cardiology and with PET in particular. And it is a game-changer because it allows us to make better diagnosis, more precise diagnosis, and more refined predictions of outcomes. And potentially, it will help us really guide management. I think what Fluorpedidas brings to the table is that because of its very high extraction compared to flow, it's a tracer that is easy to quantify, and the quantification and the validation that we have seen so far is very robust. I would also say that given the results of the exciting results of the clinical trial, I think flow will be a key addition, not an option for Fluorpedidas, but a key addition. We need to learn how to integrate what we read visually or with semi-quantitative techniques and how to integrate the flow to tell us about, you know, who has disease, who has non-obstructive disease, et cetera. But very exciting because it brings PET to potentially more patients than we can do right now and to sites, being able to really take the opportunity of the camera that they have and now have access to radiopharmaceuticals. So, I think the future is very, very exciting, and, you know, I think it will give patients a real option compared to other options that are out there. I've heard you speak about one of the issues of a very highly extracted tracer at high flow rates that in some patients we maybe see in perfusion defects that really don't represent ischemia, low flow states. I wondered if you could kind of expand on that because that's a very intriguing thought, isn't it? Yeah, I think it's a very important element for our clinical patients. You know, the high extraction will allow us to see more heterogeneity around the heart, and we're going to be picking up more defects than we currently see with other tracers, including PET and SPECT. But the question is, not all those defects are going to be representing obstructive stenosis that we think maybe should be revascularized. And, you know, issues like diffuse disease with maybe 40% stenosis can lead to flow heterogeneity that these tracers will certainly pick up. And so, the question is, how do we make accurate predictions of who would have the obstructive disease that we think should be referred to cath, perhaps should be revascularized, compared to a patient that has predominantly sort of more non-obstructive disease? And I think that's a key aspect. And the reason I'm concerned about that is because we don't want to over-refer patients to angiography that may be found to have, quote, non-obstructive angiographic disease. Exactly. So, in a sense, we kind of have to retrain, don't we, that not all perfusion defects are necessarily bad. They're not necessarily ischemic. Exactly. So, we're going to have to maybe acquire a different language of the way we describe what we see. And we're going to have to perhaps retrain our semi-quantitative techniques to have different thresholds for calling defects. And we're going to have to train everybody, including ourselves, because this is so new. And importantly, I think we're going to have to learn whether flow can really help us make our job easier about who is obstructive and who is mostly non-obstructive. I think what we learn from the O15 water literature is that the flow can have an overriding power over the visual. So, if you see heterogeneity, but your flow is above a certain threshold, don't worry. That's non-obstructive disease. And maybe the same can be done with full PDS. And we'll have to learn what kind of language to incorporate into our reports and so forth. That's so key because we don't want to confuse or reframe providers. And on the other hand, we want to give them actionable information that, you know, that they can really use for, you know, critical decision-making. Yeah. And institution of our very effective medical therapies now as well, right? Absolutely. Detecting subclinical disease may be very important. Very important. And, you know, if we integrate also the calcium into this, I think it will be a very robust approach. But it will, you know, the first fork in the road is, is there obstructive disease or non-obstructive disease? So, I think that is, we need to figure out how to do that. So, one of the interesting features about blood flow is that we're realizing that non-obstructive microvascular disease is a very important component of coronary artery disease. And one of the strengths, I believe, of fluoroperidase is that it works in both exercise and pharmacologic stress. Currently, with exercise, you're not able to use blood flow. So, how will you make that decision on which direction to send your patient? That's a very challenging question. And I think we will need more data to figure that part out. But there's at least some proof of concept that perhaps our colleagues who do quantitative, who are experts on quantitative techniques, can offer maybe surrogates that we could use that will approximate the retention of the tracer on the images to a quasi-quantification that can get us a little closer to the flow, to the absolute flow measurement. So, your concept is in the future, even with exercise, we might be able to get valuable information on blood flow? At least there's some proof of concept that this could be a possibility. And I think I look forward to seeing more of that work because it would become super relevant to this. And going back to your question, you know, we have used nuclear cardiology for many decades to only decide who has obstructive disease. Now, this helps us phenotype the entire spectrum of disease, which, as Tim said, is so important to not only define who needs a stent, but also who needs to have more aggressive preventive therapies for coronary disease. So, now, we no longer are, you know, cornered on the issue of just the obstructive lesion because most of our patients, as different registries have shown, are now showing with non-obstructive disease. Terrific. Thank you, Dr. DeCarli. It was an excellent conversation. Thank you for the opportunity. Thank you.

Myocardial blood flow

15F-loropirid

Quantification

Nuclear cardiology

PET imaging