Alicia Morgans: Hi, I'm so excited to be at ASCO 2022, where I'm speaking with Dr. Phil Koo. Thank you so much for being here.

Philip Koo: My pleasure.

Alicia Morgans: So I wanted to talk with you a little bit about radium 223, which you know, very well as a nuclear oncology practitioner and physician, and I wanted to speak about how you as a nuclear medicine physician or nuclear oncology physician work with oncologists, urologists to help think about which patients may be eligible and most appropriate for treatment with radium. So thank you for your time.

Philip Koo: Yeah, it's a real honor to be here. I think radium 223, it's been around for a while now, and I think it's still such an important drug in the toolbox for anyone who treats patients with prostate cancer. Number one, it improves overall survival. Number two, it's safe. And I think there are still misconceptions, especially in the nuclear medicine community, about the role of radium 223, still it's often seen as a drug that is supposed to decrease bone pain. Yes, that can occur and that does occur. But again, we cannot lose sight on the fact that it is a drug that prolongs overall survival.

Alicia Morgans: And I think importantly, at least as compared numerically, and these are not head-to-head comparisons, it actually looks to cause just about the same survival advantage as the other drugs that are approved in the mCRPC setting, so really quite favorable in terms of that survival advantage as well, or at least comparable. So that's helpful also. And when we're choosing treatments for patients, many people think of radium, where exactly should I put it? Does it need to be after docetaxel chemotherapy? And that's actually not the label and it's not the way that it was approved. Can you comment on that?

Philip Koo: I have an idea of why that occurs, but clearly it's not the best timing for a drug like radium 223. I think considering radium 223 before chemotherapy, I think that's where I see the greatest potential and the greatest use of this drug, especially because patients can go on to get chemotherapy afterwards. And the data clearly shows that it is safe to get radium 223 first and get docetaxel or some other chemotherapy later. So to me, it's about identifying the patients who have bone predominant disease, no visceral metastatic disease, and then consider radium 223. And that's what I think is not occurring often is people thinking and recognizing that this is a valid choice in those patients pre-chemotherapy. However, in the NCCN Guidelines, clearly they're there as one of those options.

Alicia Morgans: And what I worry about is that the earlier we are able to use radium, I think the more cycles will be able to get into a patient, and there's some data to suggest that completing more cycles, six cycles for example, is superior than completing few cycles. So if we want to really maximize the benefit from all of the treatments that we have, at least from my perspective, I want to get in as many cycles as possible of each of the drugs, and sometimes moving radium before chemotherapy can allow us to do that.

Philip Koo: Absolutely, and the data shows that getting to at least five, you get that clinical benefit and six is obviously optimal. So if you're going to start that journey and there's not the chance that you can get the five, yeah, maybe not worth starting. But if you're going to start it and you're starting it earlier, the chances of that patient getting five to six doses is very high and that's what you want. You want that patient to get those appropriate doses and get that overall survival benefit. And again, the data shows that it is a very safe drug.

Alicia Morgans: So from your perspective as a nuclear medicine physician, do you have concerns about patients receiving other radiopharmaceuticals, things like lutetium PSMA after treatment with radium?

Philip Koo: We don't have great data on those patients who've received the multiple radiopharmaceuticals. In the VISION Trial, there is some small subset of patients who have received radium in the past, probably not enough patients to draw a conclusive thought on that. That being said, we know that patients who receive radium, their counts, yeah, are typically recover and they don't really dip that much. So I think as long as their blood counts could support it, I don't see why there would be a contraindication to receiving one radiopharmaceutical, and then receiving one later down the course of treatment. So to me, as long as their blood counts can support it, it's something that we would move forward with.

Alicia Morgans: Great. Well, and then the final question is, radium 223 is actually a different type of a radiopharmaceutical than a lutetium PSMA, and one is, of course, an alpha agent, radium, and one is a beta. So can you tell us a little bit about the difference, and again, how these different mechanisms may both be useful in our patients?

Philip Koo: You know, it's the radioisotope, so an alpha particle is heavier, but also because it's heavier, it doesn't travel as far a distance. So in many ways it packs a more powerful punch, but it keeps that punch more focused so you don't hit as many healthy tissues or healthy cells as you would with something like a beta emitter, which a beta emitter particle is lighter. It does travel further distance. So it may not pack as powerful a punch and because of its lower weight, it will travel further distance. So you do get a little bit more non-target radiation delivery with a beta particle as well. I think both of them have their advantages and disadvantages and what we're clearly seeing is they both have a role in treating patients with prostate cancer.

I think the one component that we can't forget about is though how they're targeted. So the alpha particle, the beta particle is the payload, but how they're directed is based on the molecule. So you have radium 223 or you have something like PSMA. The radium 223 is going to be bone specific, so it's really going to target the bones, get to the bones, localize in the bones, and then give off its radiation. With something like PSMA, it's going to target the PSMA receptor, and then obviously give its radiation to those cells expressing the PSMA. Obviously there's overlap and there's some areas that will get some radiation delivery as well. But that's the general principle.

Alicia Morgans: Well, thank you so much. That was extremely helpful. And we always love hearing your perspective. Thank you very much.

Philip Koo: It's my pleasure. Great to be here.