 Thank you, Sandy, for inviting me to give this talk and to all of you for being here. It's especially nice for me because in my field I don't always get a chance to interact with patients as much as I'd like, so this is very nice to interact with you. As Sandy said, I work in radiology and nuclear medicine. And the outline of my talk is I'm going to try to make this very straightforward, which is that the first part I'd like to summarize some of what we currently use in terms of imaging of kidney cancer. And in the second part, I'd like to go into some of the more novel things that we're looking towards. And actually, Dr. Fan, who will speak after me, will also talk about some interesting things as well. So to go into some of the basic things that we use, hopefully most of these things are relatively familiar to you, but I'll just summarize what the role is in evaluation of kidney cancer. So certainly everyone in the room has heard of x-rays. And the benefit to x-rays is certainly that it's very straightforward and easy to use. It's inexpensive, and it's also a very, very low amount of radiation. So there's really nothing to be concerned about from that point of view. However, equally there's a lot of limitations with using x-rays, and this is the fact that it can't really evaluate deeper structures very well. And a tumor in the kidney would have to be very large before we'd be able to see it on a simple x-ray. You can enhance the x-ray a little bit by using contrast that's given intravenously, and that's why I've also labeled that the fancy term intravenous urography, which just means administering some contrast which you can see on the x-ray. And by what you're doing there, you can see that a little bit on the lower image is see the contours of the inside of the kidney that Dr. Leppert was talking about in the previous talk. But again, things would have to be quite abnormal before we'd be able to see them. And probably the biggest limitation is that if we do see something abnormal in x-ray, it always needs to be followed up with an ultrasound CT scan or MRI scan, in any case. So usually people just go straight to one of those scans. So the ultrasound is the next one that I'll talk about. It also is very easy to perform. It's a quick exam. There's very little preparation involved. Again, low cost. In this case, there's zero radiation at all. So that's even better than the minimal you get from an x-ray. And so therefore, it functions as a very good first exam. And this is often where patients are first diagnosed or some sort of abnormality is first picked up. So the exam, basically, you put the ultrasound probe over the abdomen. And what the technologist is really trying to do is to pick up areas that are fluid-filled, which kind of is the whole kidney is more or less fluid-filled. And when you have an enlargement, it can either be a normal cyst or it could be a solid tumor. And that's what the ultrasound is very nicely able to differentiate between whether it's just a cystic structure, which you shouldn't be too concerned about, or is it solid. The downsides to an ultrasound is that this technologist that I just mentioned, it's very dependent on how skilled they are in terms of being able to perform the exam. So two different technologists could pick up two very different results on the same person, and it's not very good for small lesions. Again, it has to be relatively large for us to be able to pick it up on an ultrasound. And once again, it usually requires a CT scan or MRI scan as a follow-up to fully stage what's going on with that tumor. However, again, it is a good first exam to do. Now we're getting into a bit more of the complicated exams, but again, these have become relatively well-known nowadays. So computed tomography or CT scanning or CAT scanning, the biggest advantages to it is that it definitely provides incredible anatomical detail. We can see down to things that are millimeter in size. It's not at all operator dependent. These are fixed scans that we do. And so every patient who goes in will get the same type of imaging done for them. It's very fast. The whole scan can be done within a few minutes. The downsides are it's significantly more radiation than an X or A would have. It's also much more expensive than the first two exams that I mentioned. And that the use of a contrast, especially in a patient who may have kidney issues, is something to be concerned about. Or if certainly there are allergies for the patient, that's again something to be concerned about. The use of the IB contrast though is critical in terms of delineating whether that tumor again is solid. It has what type of blood flow characteristics that it has. So it is very important to try and use that. But this is the exam that is used currently for evaluation of kidney tumors because again, it provides great anatomical detail and lots of information. And furthermore, you don't need to have a follow-up study to CT scan. Typically, you can scan the entire abdomen and pelvis and find out if there are local metastasis from that kidney cancer or not. And this will significantly help guide the surgery that will subsequently happen. So then what about magnetic resonance imaging or MRI? So here you might think that this is even better than a CT scan. And in a sense it is because anatomical detail is perhaps even a little bit stronger the soft tissue contrast as we refer to it is a little bit better with MRI than it is with CT scan. And the further advantage that it has over CT scan is that again, there's no radiation involved with an MRI whatsoever. So based on those two things you might think that this is sort of the way to go. The reason why it's not really taken over CT scanning and is considered a second line rather than a first line is because of the things listed at the bottom. It's a very, very expensive exam. A lot of people can't tolerate doing the exam because it causes claustrophobia. It's a very narrow bore that you have to go into. It's very loud. So there's those disadvantages. And since it doesn't dramatically improve what we had already seen on the CT scan, because of those disadvantages, it's not typically used over the standard CT scan with IV contrast. Okay, so to just give you one example of how all of this kind of gets put together. So this is the initial contrast-enhanced X-ray, or the urography scan of a patient. And what you're looking at is from behind. So the left side is the left kidney and the right is the right kidney. And you can perhaps make out here that there is normal contrast here in the upper part of the kidney, but then abnormal, no filling of contrast in the lower part. So there's something, again, abnormal here. So this may be followed up by an ultrasound scan, which again, the goal of this is to differentiate solid versus cystic components within the lesion and within the kidney. And again, you can see that that's what that's picking up between here and here. But then ultimately, again, this would need to be followed up by a CT scan, ideally as this one is with IV contrast. And here you can see just how much more clearly you can see this. This is all the same patient. You can see this same tumor being shown on this axial image of a large tumor. You can even pick up the fact that centrally here there's actually been some necrosis of the tumor because it's outstripped its blood supply. You can make out what the anatomy of the remainder of the kidney is, whether it's normal or not. And then, as I was mentioning, very importantly, you can look at the remainder of the abdomen and so forth and see whether there are lymph nodes that may be involved in the areas that are involved or not involved. And all of that is very critical to do. You can even extend the CT scan outside of the abdomen and look at the lungs all in one time point and look for any lung metastasis as well. So all of that is very, very easy to do. So now I'm going to start switching into some of the more novel techniques and how many people in the room are familiar with pet imaging? Okay, perfect. Very good. So I would say the majority of people are. So the key thing to keep in mind about pet imaging, which is positron emission tomography, as compared to everything else that we talked about so far, is that this is not looking at anatomy. It's looking only at function. So you're actually looking at cells and the distribution of the cells within the body. And so depending on which specific tracer you inject, so whenever we talk about pet imaging, we don't just talk about pet. We'd also talk about the tracer that's actually injected. So John mentioned, you know, the tracer that he was using for fluorescence imaging. It's a very similar idea here, is that depending on which tracer you use, it will specifically go and home in on certain types of cells and not others. So the most common type of tracer that we use for pet imaging is called FDG, fluorodeoxyglucose. So it's basically a radioactive form of glucose. And so what that means is any cell that's taking up a lot of sugar and cancer cells will generally take up more sugar than will non-cancer cells, then we can see those specific types of cells. So that's a very important thing to keep in mind because when you look at the scanner, as you are, it looks very similar to the CT scanner or the MRI scanner, but it's inherently a very different type of machine. Now the downsides to pet scans is kind of similar to what we mentioned for CT scans. Again, this is a radiation exam. Primarily the radiation is coming from the injected radiotracer. Also it's an expensive exam. And one of the downsides specific to kidney cancer is that with the tracer that I said is most commonly used, FDG, it actually doesn't do a very good job of looking at the kidney itself. But it does an excellent job of looking outside of the kidney to see where else there might be disease. So I just want to highlight this point again that we're no longer doing anatomy with this image. So this shows you exactly what we actually do is we inject this radioactivity usually into the arm. It circulates around the body. We wait about 60 minutes or so for it to go where it wants to go and also to let it clear out from the body as well. And then once you're in the scanner, the scanner itself is not emitting any radiation. It's the patient now who's emitting all the radiation and the scanner is just picking up that radiation to see where did those molecules of radioactive glucose go once it was injected inside you. So these are some of the images that we can get from this. And again, what this is showing you, these are just different views of the same patient. What this particular image is showing you is that we can't evaluate the kidney itself well for various reasons that kind of go beyond the scope of this talk. But these other arrows are pointing out the areas of metastasis very far away from where the original tumor was. And this would have been very hard to pick up on standard anatomical imaging. Often even if you looked at that area on a CT scan or an MRI scan, you may not actually pick up anything abnormal. The major advantage to this is it's very, very sensitive. It's much more sensitive than a CT scan or an MRI scan for small amounts of tumor. You would have to have a large amount of tumor in a different area for it to cause an anatomic deformity in that area for a CT scan or MRI scan to pick it up. So that's where the real role of FDGPET in particular is, is to look at the whole body and to identify all the areas that are involved potentially with disease. So as you can see from these images, one downside to it is it's a little bit hard to actually tell where you are within the body because, again, this is all just looking at cellular uptake rather than anatomy. And so one thing that's been done since the early 2000s is that no PET scanner actually has been sold since then without it being attached to a CT scanner. So ever since then, people obviously realize that well if you combine the CT scanner, get the anatomy and you do the PET scan and get the functional imaging, then you get the best of both worlds. So this is just typical image of what we see. Here's the whole body PET image and this is an axial PET image and then we combine it with an axial CT scan and we actually do a fusion overlay. The computer automatically does it. Since the scanners now come with the PET and CT component together, it's very easy to simultaneously acquire these images and this is why when you've had it done, we've asked you to lie very still if you can so that there's no movement between the CT portion and the PET portion and for small lesions we can really identify exactly where that was. The other thing PET imaging is very good at and again I would argue that it's significantly better than anatomical imaging is looking at response to therapy. So this is of course very important for everyone with cancers that once you've been treated how do you know whether the treatment is actually working and what you can see on these serial images so that this is labeled at baseline, this is four weeks after therapy, this is after 16 weeks of therapy and you can just, anyone in the room can pick out that there's a lot of lesions here, a lot of black dots that have improved on the middle scan and that have improved further on the follow-up scan and further to drive home the point you can see on this images that here's the baseline scan here's the four week follow-up scan and on the CT portion of it which is under this fusion it actually doesn't look any different at all both in this pulmonary nodule and in this lymph node here in the front of the medius dinom and however you can see that the FDG uptake has decreased dramatically so this is showing you the power of the response assessment with functional imaging which normal anatomy often is lagging behind a long time it's not that this is not going to show improvement it would take much longer to know and we want to know right away whether a treatment is working so that we can either continue that treatment or change that treatment as needed so to conclude I'm going to go into some of the newest technologies that we have for, is there a question? it's all kind of in the same realm I would say there's a question is can we do a PET scan more frequently than we can do anatomical imaging and I would actually say that it's all about the same because remember there is still radiation associated with doing that exam it's about equal to doing a whole body CT scan yeah and then yeah exactly and then not to get into it with of course there's insurance issues and so forth and so they only allow every so often but even medically I would say that it doesn't necessarily make sense to do it do things too often because then you pick up other things which may not be relevant the radio tracer that we use actually has a half-life of two hours so after about one day it's gone anyway so we have to inject again so one of the main areas that is a focus of research for us in imaging is to use novel radio tracers so I mentioned the radioactive glucose that's been used now believe it or not for almost 20 years a little over 20 years actually and no other radio tracer has been able to really overcome how good FDG already is but over the past several years there's been a lot of very interesting work going on on new things that highlight specific other types of cellular activity rather than just the glucose so I'm going to highlight two of them in the remaining amount of time I have one that is really up and coming is called glutamate imaging this is a very complex slide and all I mean to show you with it is that this glutamate molecule within the cell you can see that it has a very central role in many different functions within the cell so the idea being that if you could image noninvasively what's going on with that glutamate that would be very interesting to know what's going on and again we think the cancer cells have much more glutamate than do other types of cells and secondly if you can block that glutamate from being within the cell then you could potentially block the cancer cells from growing as well just to... well yeah you're never able to block everything but you preferentially are blocking it in the cancer cells over the normal cells because they have much more of that glutamate than do normal cells this is just to show you how many this is just a very small number actually of the articles that have been published within the last few years looking at this glutamate and how it functions within the cell just to show you how much interest there is in cancer research related to glutamate imaging and glutamate is such a new radio tracer that we actually haven't even imaged anywhere in the world a single patient with kidney cancer but we are actually a brink of doing that Dr. Srinivas and I and Dr. Fan are working on the first clinical trial for this tracer which is called FSPG in kidney cancer patients but I'm going to show you some images from some of the patients that we have imaged just to show you how interesting it can be so this first group of patients that you're looking at actually have brain metastasis from lung cancer so you're looking at images of their brain all these images on the right hand side are with the standard tracer FSPG and the ones on the left hand side are with FSPG and so you can I think very easily make out how much easier it is to pick up the cancer with the FSPG so this area versus this area and then these two lesions here within the brain you can't even see them on the FSPG at all but they're incredibly bright on the FSPG just to show you how much more sensitive and specific this tracer can be compared to FSPG here's another set of patients these are patients with head and neck cancer and so same idea these are the ones with FSPG and again you can see that it's very easy to make out the tracer uptake on the FSPG images compared to the FSPG the only exception actually was this patient who had more uptake on the FSPG and interestingly it turned out that this was not a real recurrence of the cancer but just some infection within the area of prior surgery and so actually it turned out that the FSPG in this case was also more sensitive than the FDG because it actually told us the correct information rather than that's one of the major downsides of FDG which if you've ever read any of our reports we're always hesitating between whether calling cancer or calling something inflammation which is a big deal of course to you or to anyone else and we're very aware of that but that's the limitation of the tracer we sometimes just can't tell whether something is real or not I mean you look at this image here and it's hard not to call that but how do you know whether that's infection or not and then lastly another tracer that one of my colleagues is working on angiogenesis, angiogenesis is the development of blood cells new blood vessels into tissue and cancer cells heavily dependent on this because as they are growing they need the blood supply to bring in oxygen and so forth so same exact idea as that one is on one hand it would be good to image that and be able to see where are the areas of new blood vessel growth going on within the body and secondly if you could block that with certain chemotherapy agents then you would be able to block the cancer growth so what we're trying to do as you beginning to see now is to tie in specific imaging to specific therapy and this is a field called theranostics because we're able to do therapy and diagnose disease all at the same time so just a couple of examples of this this is again such a new tracer that hasn't yet been looked at in kidney cancer and this is a patient with breast cancer who had metastasis to different parts of the body and these are the angiogenesis imaging agent and this is the FDG again you can see that this is showing much more uptake on the new tracer than it is with the FDG and this is not meant to say that the FDG images are not useful but they're telling you two very different things the FDG is telling you where there are areas of increased glucose use and the angiogenesis one is telling you where there are areas of increased blood vessel development so now if you're trying to give that a specific patient a specific therapy that blocks the blood vessel growth you can say that they probably won't work so well for a certain patient versus another patient if you can identify whether they have this uptake or not here's another patient imaged with the angiogenesis agent who had brain cancer again you can see it's showing up much more nicely with the angiogenesis agent than with the glucose and as I mentioned with FDG as well this is showing you how you can follow patients who have had therapy before and after a drug that blocks blood vessel growth and you can see that the uptake is going down as well so that actually concludes my talk and if there are any other questions I'm happy to take them