Renu Eapen: It's amazing, isn't it? And it just goes to show, Zach, how far we've come in the last 10 years. So while I was preparing my talk, I did a little ChatGPT search, and said, "Search ASCO 2016. How many abstracts were there?" One, in prostate cancer. And it was a small, retrospective series from Germany just on their initial experience with lutetium-177-PSMA-617 use. So now fast-forward 10 years, a whole session on this.
Zachary Klaassen: Amazing.
Renu Eapen: And not even about current things, but what's happening in the future.
Zachary Klaassen: Absolutely.
Renu Eapen: So it's super exciting.
Zachary Klaassen: And you're setting the stage. You set the stage for this session with overview talk. Part of it's on where we are right now. So what were some of the highlights from that first part of your talk?
Renu Eapen: Yeah, there's so much out there. All the pivotal randomized trials that have happened in this space, the trials that have stamped lutetium-177-PSMA-617 as the standard of care in mCRPC and showing promise in the earlier setting. So I really am trying to just put all that data into context. So what I was trying to do was look at the journey of prostate cancer from localized disease all the way to advanced mCRPC third-line treatment, and see where the trials slot in and what would be considered standard of care at this point. All the way forward to even the LuTectomy-
Zachary Klaassen: Exactly.
Renu Eapen: Neoadjuvant trials. So it's really just showing, look, there's so much evidence out there, but where is the use now standard of care an approved tick? Where is it still a bit of a contentious issue? And currently there's lots of great trials, but perhaps not standard of care just yet?
Zachary Klaassen: And Peter Mac has been at the forefront of all this, so I think you're the perfect person to set the stage for it. The second half is basically where are we going? So where do you see the field going over the next five to 10 years?
Renu Eapen: So I think the time to think beyond PSMA is upon us. So looking at new targets that we can exploit for, not just for imaging, but also radioligand therapies. And this has been a focus of investigation now for many years and now we've got 10 or 11 potential targets, some of them even better than PSMA. So I think radionuclides that target these new proteins are being developed and are in phase 1 trials. So I point out three of my top front-runners that I think will make an impact in the future: APC, STEAP1, 2, H7B3, and then new isotopes. And we'll hear about some of them in the session, especially actinium, but also lead, copper, which now is used in imaging a little bit in early trials, but will have theranostics implications. And then combination therapies, which I think will be the future for lutetium-177-PSMA-617; understanding what agents will enhance the effects of lutetium-177-PSMA-617, which are the radiosensitizers that it works well with? And the biggest point is that all these translational and biomarker work that's embedded into these clinical trials will help us understand which combinations are going to be most powerful.
Zachary Klaassen: Yeah, great summary. You mentioned something about these new targets. So PSMA is on the prostate, but we've also got DL3, we've got STEAP1. Just talk about for the ... Because even at a lay level, what does that mean? We've been targeting PSMA forever, but now we have other targets. What do you think that means going forward?
Renu Eapen: I think the promising targets will be the ones that have the lowest levels of salivary gland uptake. So the biodistribution of these targets are going to be really important. So that's where those initial trials are going to be key. And then we want targets where uptake will correlate with disease aggressiveness. And I think those two things are going to be the key when we select these new targets. So PSMA is very good, but we do see now that lutetium-177-PSMA-617 has been in use for many years. We're starting to see what the long-term toxicities are, and what we want to do going forward is use these targets in a way that we can minimize toxicity.
Zachary Klaassen: Yeah, that's awesome. You mentioned at the second half of your talk, where are we going next? Let's just say, what are your things you're most excited about the next three to five years?
Renu Eapen: New isotopes, for sure. I think copper is going to be very big. I think its potential for therapy we've seen through the initial trials that look at imaging. Louise Emmett released the co-PSMA trial in European urology recently. That's going to be very exciting. Terbium-161, it was presented the first in human study, the VIOLET trial was presented.
Zachary Klaassen: Really cool, yeah.
Renu Eapen: Yeah, really cool. Very much like lutetium-177-PSMA-617, but has those extra Auger and conversion electrons. That I think will be really interesting to see where that goes. So the new isotopes I think are really interesting. The combination treatments, LuCAB, combination of lutetium-177-PSMA-617 and chemotherapy, combination of lutetium-177-PSMA-617 and radiotherapy, the LUNAR trial, POPSTAR, all of those things will be really exciting. And I really do think these target's going to be very cool. H7B3 I think is going to be really interesting.
Zachary Klaassen: Yeah, absolutely.
Renu Eapen: So yeah, we're at the start of the journey.
Zachary Klaassen: I know, exactly.
Renu Eapen: It's very exciting.
Zachary Klaassen: I'm so glad you mentioned 2016 to '26. It seems like a short amount of time. It feels like the dark ages now.
Renu Eapen: Yeah.
Zachary Klaassen: Anything else we haven't hit on? Anything you want to mention before we wrap up?
Renu Eapen: Look, it's been a great conversation already, Zach. In fact, the session is so great that the SNMMI conference that's happening in LA at the moment, Michael Hofman and Professor Jacene dialing in live into the session at ASCO.
Zachary Klaassen: That's awesome.
Renu Eapen: So I think it'll be great. And the ProsTIC theranostics preceptorship is going to be happening in Melbourne this year. So a very warm welcome to all your listeners out there. Everything you never even realized you wanted to know about Theranostics, you can find out in Melbourne.
Zachary Klaassen: Perfect. Great chatting with you, Renu, always.
Renu Eapen: Thank you so much, Zach.
Zachary Klaassen: Thanks for joining us here today.