 I think there's maybe some questions and some Q and A and I will, I'm going to start taking those, maybe first come first served and hopefully I'll get as many of these answered in the next 15 minutes or so. All right, so it looks like the first question was, what's the threshold PSA after prostatectomy can reliably detect recurrent or metastatic disease? So this is a controversial topic but I think a very good question. So certainly if you wait longer and as a PSA goes up your chance of the scan being positive is going to go up. But of course the chance that the patient also has disseminated disease and isn't going to respond to salvage radiotherapy also goes up. So what I generally tell our clinicians and our clinical practice pattern has been that if the clinician is going to pull the trigger on a salvage therapy they should get the PSMA scan first. Nothing's worse than say doing salvage radiation for a patient and then their PSA keeps climbing and then eventually we get a PSMA scan and sure enough they had a lymph node that was outside of the salvage field. So no matter what the PSA is if salvage radiation therapy is going to be the next step probably need to get the PSMA scan first again before just not to have any regrets later. It doesn't mean that the scan is going to be positive we may not see the site of disease but we at least know that we weren't sitting on sort of a deal breaker lesion that we just missed because we didn't image. I would say insurances can have problems with imaging at PSAs below 0.2 because all of the data we have is at 0.2 and higher post prostatectomy. So it isn't clear exactly how insurers are going to cover that but from a scientific standpoint I think we're justified to scan patients so long as it's before the next step in their therapy. And then the next question that I can PSMA pet replace MRI for making a diagnosis of local staging. I would say they're complimentary. It's hard to see EPE for instance on PSMA pet it is relatively, you know it's at least possible to see it on MRI. I think PSMA pet is very good for some malversal invasion. That's a little anecdotal but it just seems like it's really good for some malversal invasion. But what PSMA pet really gets you is the sort of local regional staging the public lymph nodes that may be too small to call an MR. And then of course it gives you a wider field of use systemic staging. In an ideal world, I suppose we don't have really nice pet MRs but not every place does and not every place will. So I do view the modalities as complimentary and I think it makes a lot of sense for patients to get both if that's possible. Let's see, do you try to do initial staging PSMA pet before giving ADT? Again, you know, I guess if the patient's gonna get systemic therapy no matter what the PSMA pet may not add a ton of value. I think the real value of PSMA pet is trying to find those patients who have low volume metastatic disease or local regionally recurrent disease that may have sort of salvage options like SBRT. But to really get an idea of a patient's extent of disease I do believe in sort of PSMA pet before initiating systemic therapy just because the PSMA pet's gonna be hard to interpret after the systemic therapy. As you sort of saw in a couple of examples the lesions can do all sorts of things. So it is very hard to interpret PSMA pet right after the initiation of ADT. So I'd certainly prefer to have it before than just have it after. Is there a way to compare the FDG and PSMA scans for progression or response to ADT if a patient's undergone FDG prior? Yeah, you know, if a patient's disease is FDG avid and many castration resistant patients will actually have a fair bit of FDG avidity. I think you can follow them by FDG and that's probably a decent way to follow them because their disease is going to be from that point on, glycolytically active. And so if you see that loss of glycolytic activity I think that's actually a good way to follow them. A combination of PSMA and FDG unfortunately buddies the waters quite a bit. So I'm not sure exactly how to sort of take the combination of the two of them. Like if you saw sort of new lesions on PSMA that weren't FDG avid, would you believe them? I guess I would, but it is certainly hard to follow with both modalities. We don't have great data on following with both modalities. So if they have avidity on one I would probably try to stick to that one and follow them all on those lines. All right, use of PSMA and initial value issues patients found on screen to have elevated PSA and may not do well with MRI screening. Yeah, so there's a little bit of data on this. There's a trial called the primary trial from Australia uses Galli and PSMA 11. And they reported that the PSMA was actually a little bit better than MRI at finding clinically significant disease. I can tell you my anecdotal experiences that they almost always find the same thing if there's clinically significant disease. I don't know that I find PSMA upfront as definitively better. Although again, they always sort of publish literature would say that it's at least a little better. In terms of patients that can't get MRI screening I think the big holdup would be insurance. I think insurance is now pretty cool with MRI as sort of a secondary screening modality for patients with elevated PSA but there are no guidelines that recommend PSMA PET in that context. And in a patient who in fact the guidelines specifically say PSMA PET is only for men with prostate cancer. So an insurance company would have a pretty solid foundation to stand on to say that this patient doesn't have confirmed prostate cancer or we're not gonna pay for their PSMA PET. However, if insurance is okay with it then I think it can be a very useful adjunct to MRI. MRI is probably still the gold standard in that space at least in my mind based on the level of data that's out there. But it is for a patient that maybe can't get an MRI if you can't get a PSMA PET, it can't be useful. All right, do I have experience with Pazluma and what I consider an equivalent to Polarify? So yes and yes. So I've read, I don't know, probably 80 or so Pazluma scans that were done on various trials and whatnot and my experience with it is pretty much exactly as the companies describe it or at least someone as they describe it. There is less urinary excretion than Polarify. So I do think you potentially get a little bit of an improved look at the pelvis. There's probably a little bit more false positive bone uptake. Again, that's anecdotal. I don't really have data on that, but my observation was I would sometimes see things that I was sure were benign but lesions that seem to have Pazluma uptake. Of course I don't have head to head necessarily Pazluma and Polarify scans and any significant number of patients. But yeah, my impression from the clinical trials that were done is that they are statistically equivalent and we should, from a guidelines perspective and use of them in different indications, we should be comfortable with either one. Can you share your protocol for PSA imaging for Polarify? Do you think that imaging in two hours has been official? Another great question. I think that there are occasional lesions that show up at two hours and don't show up at one hour. And it is possible that it is possible that that may make a difference in one patient or another. You never sort of know there's not necessarily like a big prospective trial that has shown that. I would note that two hours is outside of the FDA approved label for imaging with Polarify. I believe the Polarify label is something like 45 to 90 minutes or something like that. I don't think it goes out to two hours. So it would potentially be off label to use it at two hours which is not a big deal, just something to be aware of. What I think is maybe the more practical consideration is that at two hours, you've used an uptake room for two hours and that may not work with your pets in our workflow because everybody's getting image with FDG at one hour. So we use one hour because it fits in with our FDG workflow. And I think it's an uncommon patient that's gonna benefit from imaging at two hours. If you do have the option though, there may be occasional patients for him that would be beneficial. All right, if PSMA scan is negative of patients with a rising PSA, following initial treatment, have you found FDG scans be of any value? No, I think FDG only really becomes a value when you've got relatively advanced castration resistant disease. There are certainly FDG positive tumors that occur before that, but they're relatively uncommon. And I suppose a question could also be asked, is AXMEN useful in that case? I tend to think not either because I think most of the negative scans and PSA in that patient population are because of volume of disease and there's no molecular imaging that's gonna find them. So the question is whether a negative scan then triggers salvage radiation therapy still or what we should do with that negative scan. But I think right now in the guidelines level data would I think support the statement that PSMA is the most sensitive modality that we have for the biochemical recurrence setting and that there's no real reason to believe that other modalities are going to be reasonable problem-solving tools. There's one exception I think to that. In a patient who may have a local recurrence, maybe they have a positive margin at surgery, I name it contrast-enhanced pelvic MR is a great tool. So if you don't see anything on PSMA in that context, a multi-parametric MR is maybe still a great option. All right, if there is an equivocal transitional zone finding is PSMA-positive side biopsy versus active surveillance. Yeah, I'm not aware of any data that would suggest that. There is data that PSMA-PET can make you more confident kind of in reading the MRI. So if you did, yeah, I can certainly imagine a case where you've got something on MR, it's Pirates III, what do you really do with that? It's blazing hot-on-pet that you go ahead and biopsy that. Pattern for disease seems to be important for PSMA uptake, at least somewhat. But again, yeah, I'm not aware of prospective data. So it would, again, I think insurance issues may sort of come into play, but it would be a reasonable step from a scientific standpoint. Let's see, anonymous attendee, do you recommend stopping ADT for some weeks before doing PSMA-PET? We don't, whatever the patient's on, we figure that's sort of the state of their disease and we should go with that. So if they're on ADT and they've got a rising PSA, that would indicate they have viable disease and it's progressing, it's likely to be PSMA avid, and we should go ahead and image them and take a look if it's sort of otherwise reasonable to image them. So yeah, we don't really try to change anything that the clinicians are gonna do. Again, I think it's not always a great idea to try to scan them right after initiation of ADT because weird things can be going wrong, but we don't stop ADT generally. Okay, so Pirate Street Peripherals and Lesion, is PSMA useful to side biops or not? Again, I think it could be helpful, which again is extrapolating from data that isn't exactly in this space. I think it could be helpful, but I would, and if the patient has no prostate cancer, even if it's, well, I guess the problem is anybody that's on surveillance is gonna have at least favorable intermediate risk and the guidelines don't recommend PSMA pet in that context. So again, insurers may have a problem with that. I don't always know how nuanced they're getting with things, but I can imagine insurance being an issue there. And then maybe a time for one more question here, and I think there's about one more question here. So are we administering Clavicto? Do you think metastatic constriction that doesn't submit or refuse chemo could be considered for therapy? So the real problem there is that the data that shows that men who are not post chemo and their benefit of Clavicto hasn't been published yet. And so I don't believe an insurance company is going to pay for a $300,000 course of Clavicto on that basis. It's really the FDA label only for post chemotherapy men. So while I think that we're gonna move into an era very soon where we're giving Clavicto pre-chemo or in men who don't want chemo, we're not quite there yet. So we are only giving Clavicto right now to men who have progressed on chemotherapy. Okay, and then one last question. So I said one more, but we'll do this one. Do you handle focally intense bias may uptake without CT correlate? So it depends on where it is. If it's in bone, I look really hard for a CT correlate because sometimes the CT correlates are very subtle. They may be like, something that's maybe minimally expand style, there might be a good fit for fibrous dysplasia. If, so in bone, I think it can be tricky, but if it's really intense, we do have to take it seriously. If it's outside of bone, if it's in soft tissue, I guess it would be very case dependent. It was truly out in the middle of nowhere and there's no lymph node around. I wouldn't be sure what to think of that. In other organ systems, it may require additional workup like if it's in the liver, that could be an HCC or something, it may have to go hunt that down a little bit. But yeah, it would sort of depend a little bit. And then if it's in the prostate, it's almost certainly prostate cancer and that's presumably, I guess, why the patient would be being imaged. And with that, I do apologize. I will gonna have to run. I know there's probably other questions that'll trickle in, but it's really been a pleasure joining you today. And I hope this was a useful talk and I really thank you all for your attention. Thank you for some great questions and hope everybody has fun reading these scans.