Rethink Imaging

EP 36 • January 22, 2026

Bringing Advanced Cancer Care to Community Hospitals: Building a Theranostics Program

Featured Guest

Dr. James Cassuto, MD

Director of Nuclear Medicine; System Associate Medical Director of Nuclear Medicine, Atlantic Medical Group • Overlook Medical Center (Atlantic Health System)

Listen Now36 min

Also on:

Let's Talk

Beyond dose

Ask us what your imaging data can actually show you.

Start a Conversation

Share This Episode

Subscribe to Rethink Imaging

Theranostics moves fast in headlines, and the harder question is what it looks like when a real health system runs it for real patients. Dr. James Cassuto, Director of Nuclear Medicine at Overlook Medical Center, joins the show to walk through how molecular imaging now guides cancer treatment, not just diagnosis, and how he built a program that delivers academic-level care close to home so patients do not have to travel for it.

The conversation stays practical. Cassuto explains the core idea behind theranostics, using the same molecular target to both find a cancer and treat it, and why patient selection is where outcomes are won or lost. He describes how post-therapy imaging tells the team when a therapy is working, when to pause, and when to change course, and how that reduces unnecessary toxicity and gives patients more good time between treatments. He also covers the realities of standing up a program, from internal approvals and radiation safety to staffing and workflow, and looks ahead to expanding tracers into new uses such as brain tumors and vascular targeting.

Host

Chris St. John

Host, Rethink Imaging • Imalogix

Featured Guest

Dr. James Cassuto, MD

Director of Nuclear Medicine; System Associate Medical Director of Nuclear Medicine, Atlantic Medical Group • Overlook Medical Center (Atlantic Health System)

Watch the Episode

Key Takeaways

Theranostics uses the same molecular target to diagnose and treat a cancer, which turns imaging into a treatment decision tool rather than only a diagnostic step.
Patient selection drives outcomes. Imaging shows which patients are likely to respond, which makes the right treatment more important than more treatment.
Post-therapy imaging guides timing. It tells the team when therapy is working, when to pause, and when to stop, which helps reduce unnecessary toxicity.
Imaging-guided care can extend treatment-free intervals and improve quality of life, sparing patients side effects like neuropathy, hair loss, and nausea from later-line chemotherapy.
Community health systems can run theranostics at an academic level. Building a program means working through approvals, radiation safety, staffing, workflow, and financial planning.

Full Transcript

James Cassuto Transcript

[00:00:00] Chris St John: They’re showing some of the pictures of these patients, and my mind was blown on the spot. You had patients with horrendous disease, large volume disease. They gave them this therapy, and it was like it melted away. And I saw that, I said, you know what? We’re in an age now where we’re starting to see new pet tracers come out.

[00:00:18] James Cassuto: We’re here because we’re curious about medical imaging or have a hunger to learn more. What can we learn from each other, and how should we prepare to tackle the challenges ahead? I’m Chris St. John, and join me today as we rethink imaging, a podcast by Imologix. Welcome to the show. Welcome back to rethink imaging recently rebranded. We dropped the frame by frame, so now you all can find us much easier. Today, I am joined by doctor James Casuto, who is the director of nuclear medicine at Overlook Medical Center and the system associate medical director of nuclear medicine at the Atlantic Medical Group. James has built one of the region’s leading theranostics programs using molecular imaging not just to diagnose, but also treat cancers. He’s been recognized by radiology business as a 40 under 40 honoree and by the American Cancer Society for his work bringing advanced cancer care to patients close to home. James, welcome to the show. I am so happy to have you today.

[00:01:17] Chris St John: Thank you. Happy to be here and appreciate the opportunity to speak with you guys.

[00:01:20] James Cassuto: Yeah. Of course. Which, funny enough, I don’t remember if I told you this when we spoke originally, but I was actually born in Summit Overlook Hospital.

[00:01:30] Chris St John: Alright.

[00:01:31] James Cassuto: Yeah. So silly small world thing, but I came from the very place where you are building this program. So let’s get into it. Can you lay a little bit of a foundation for me about theranostics beyond its status as a portmanteau, a hybrid word, and what is going on with it right now?

[00:01:49] Chris St John: Sure. Yeah. So first great characterization of the portmanteau. I had to look that up myself. The fabulous word, and I think it encompasses what this is. So it’s the idea that we can diagnose conditions and we can treat conditions with, um, essentially, molecular probes. I’m on the radiology side, the nuclear medicine side too. For me, this is nuclear thegnostics. But in general, if I can show that certain cancers are expressing cell receptors on their surface or certain proteins associated with them specifically, and then we can guide therapy specifically to those therapy to those receptors, that’s what theranostics is in a nutshell. If I can show that breast cancer patients have estrogen receptors at the tumor level, then we can treat with anti estrogen type medications. From the nuclear medicine side of things, it gets a bit more interesting in my opinion because we can take a molecular probe targeting those specific attributes of the cancer cell, whether it’s a protein on the surface, whether it’s something in a tumor microenvironment. And if I can show an imaging that there’s enough density of those markers and I can get enough of this small molecule to those areas, I can make them radioactive from a therapeutic standpoint. So instead of doing something like a PET scan, which is using radiation for radioactivity for imaging, we can make those same molecules radioactive in a different way to emit beta emitters when deposit massive amounts of radiation therapy only to those types of cells. So this really lets us target only cancer cells, leave the surrounding tissue alone, and we wind up getting great outcomes without the systemic side effects we’re typically associated with things like chemotherapy?

[00:03:22] James Cassuto: Okay. So I think I get the basics of it, but this is all still very new for me, so you’ll have to forgive me as I’m catching up. So we’re there’s the diagnostics and the therapeutic side of that portmanteau for our listeners. Portmanteau, two words coming together. So you are using your scans to find these cells and mark them in the imaging? And I keep reading and hearing the term marking the cells. What is actually happening when they’re marked?

[00:03:51] Chris St John: So I guess if you think of it like a key with a key chain, we got a whole bunch of doors that this could potentially go to. That key will only fit into one door. I’m looking for a key the door that’s the cancer cells. If I find a molecule, the key that’s going to go there, I can switch what the key chain is. I can make the key chain a pet tracer, like f 18 that that I can see on imaging, but I can leave the key alone. That’s the marking the cell part. And then we can exchange that key chain for something else that’s radioactive like a beta emitter. Use it for cell destruction and death, and that’s what we use to treat the the lesion. So, essentially, we’re trying to and every cancer winds up being a bit different. So just because we say, well, this is a prostate cancer, it should have the prostate cancer marker. Some cells do, some cells don’t. Even in the same patient, some tumors do, and some tumors don’t. So our job really is to figure out which patients have the certain type of tumor that is amenable to being kinda tagged or labeled with these cancer specific agents because those are the ones we could then use for treatment.

[00:04:48] James Cassuto: And the cancer specific agents, what are those?

[00:04:52] Chris St John: So there’s a company called Novartis. They make something called Plavicto that goes to prostate cancer. They make a drug called Lutathera that goes to neuroendocrine tumors, specifically the somatostatin receptors. There’s a drug by Bayer called Xofigo that goes to breast cancer bone metastasis, and then there’s a drug, I one thirty one, that’s radioactive iodine. It’s been around since the forties, really. But those are kind of our theranostic type pairs. Xofigo’s a little different. It goes to sites of bone turnover around metastasis. So instead of finding a cellular marker specific for that for imaging, we’re using a bone marker for bone turnover. But the idea is the same. If we can prove with imaging that the mechanism for taking up these therapies exists, then I can send the therapies in.

[00:05:33] James Cassuto: I think I got it what’s going on. So I’d like to backtrack a little bit now that I have my foundation laid and ask you about your relationship to theranostics. I believe you once said, while still experimental, you knew this was what you had to be involved with, what is now coined nuclear theranostics. Can you tell me a bit about the lecture where you first heard about using these tag molecules and the effect that it had on you?

[00:05:59] Chris St John: Sure. So I went to residency for radiology. I was interested in doing intervention radiology as a procedures. And then there was an early on in that training lecture by one of our nuclear medicine physicians about an older drug called Zevalin, which was used for lymphoma. But the idea then was that, uh, you could target these lymphoma cells with the y 90 version of the sarnostic pairs. And I had never heard of that before, never seen it before. By the time I was in training, that therapy had kind of fallen out of favor a bit, but they were showing some of the pictures of these patients, and my mind was blown on the spot. You had patients with horrendous disease, large volume disease. They gave them this therapy, and and it was like it melted away. But I saw that and said, you know what? We’re in an age now where we’re starting to see new pet tracers come out specifically for disease, not necessarily for therapy at the time. But I kept thinking, man, all you have to do is make them the other version of radioactivity, and then you’re gonna wind up changing cancer care. And that reminded me a bit about what I had seen even before that in research, not realizing at the time, but we were making these kind of protein labeled sugar molecules that we could detect on imaging. Someone was using it to localize the sites of MS to try to deliver therapy. This was over at, uh, in Oxford where I had done some research. Our lab was using it with inflammatory markers. You know, now maybe twelve years since then, those types of technologies are coming into favor. They’re no longer fringe, and this is becoming more of a mainstream kinda cancer therapy.

[00:07:21] James Cassuto: Yeah. And so when you say appear in imaging, are you still reading these images traditionally, or is there technology aiding with you or aiding you when you’re interpreting the images?

[00:07:33] Chris St John: Good question. Technology is there to help aid. Our systems in the process of buying software to help us read it. Right now, I’m reading it as I would kind of traditionally, I think, as most people are reading their PET scans, which is the patients come in, they get injected with the radio tracer for imaging, they incubate for a bit. The images are taken, and then we’re reading them. When we’re looking from a prognostic standpoint, who’s amenable for treatment, we wanna see patients that have very high uptake of these tracers. But very high is a qualitative kinda subjective word. And and even in literature, some say this is high because it’s brighter than the liver. It’s high because it’s brighter than the salivary gland. It’s higher because it’s above some number that we’ve established as being a threshold from a relative kinda uptake standpoint. But, ideally, I’d love to be able to go through and say this patient has 1,500 ccs of tumor, x percent are expressing these particular markers to a certain extent that we know can allow us to get enough radiation therapy into have a meaningful response. And that becomes the trickier part. So you have patients that we treat. We know you at least you’ve got some lesions that are gonna be amenable to treatment, some are not. It’d be nice to quantify. It’d be nice too in the future. And I think we’re on the way to get there, but the field is developing as we speak, which I think is one of the most exciting parts about it. But as new treatments come out, as these technologies are developed, we’re not too far off. We can auto isolate the or auto segment rather the the lesions on the imaging, kinda characterize them by what is or is not appropriate for being treated. We know that the amount of radiation that these tumors absorb is in somewhat proportional to the kind of kill response we’re going to see. Can we calculate if the tumor volume we even have with the uptake it’s showing can even be destroyed by these therapies? And if it can, great. If not, we know before we even start that these are patients who need to be on a different type of drug. So these type of your pretreatment imaging, your kind of pathways are really important, and they’re helping us select which patients are gonna get treated, which patients shouldn’t get treated. If there’s a future where we have combo drugs or kinda cocktails, then we can say, great. The differentiated tumor gets treated with the standard Plavicto and these other lesions which won’t be seen or don’t have enough uptake. I can target the tumor microenvironment more of a differentiated kind of tumor, and I think that’s where we’re gonna it’s going to see this going. It’s not just to help us read the scans and kinda make us more efficient, but it’s gonna help quantify and really make this an objective evaluation of who should get what and when that should be.

[00:09:56] James Cassuto: Right. And I’m glad you’re talking about who, what, and when, because you’ve pointed out that before your program existed, patients often had to travel or lacked access to the kind of imaging to therapy workflow that you now offer. What kind of gap did you see in your region that you were like, oh, the we have to do this here at Overlook?

[00:10:18] Chris St John: So the biggest gap is is going on the map and going to some of the drug company websites and seeing, you know, you know, to kind of find a center app, and then you you look and say, wait a minute. There’s red dots all around where I am, but not where I am. I mean, I wanna see the physicians here and say, where are your patients going? Where are they getting their care? And they’re telling me, well, New York City might only be 20 miles from here, but that’s a two hour drive if you’re stuck in traffic, you know, for some of these therapies and same freak out and trying to get down to Philly sometimes. So that kinda showed that the need exists. I know patients will be in the system to get care in as they should. We’re not gonna hold patients hostage until someone comes along to do this. But if we can get a program that that doesn’t just provide the services, I’m not excited by that. I want a program that provides the services and makes you wanna stay here, not because you geographically kinda have to, but because I’m gonna give you the same care you’re gonna get at a big academic center. I mean, that’s what was the impetus for starting it here. It’s not just a line item or a checkbox for the hospital to say that we can do this or for a department to say, look. We’re just the dispensary. It was to take ownership of what the technology was for the region and turn it into a a referral hub, you know, someplace where peace when patients wanna come as a destination, and I think that’s what’s made it as successful as it has been.

[00:11:25] James Cassuto: Yeah. And so when you decided to start this program, like, how does one even go about doing that? Who do you need to talk to within your facility, and what are you actually saying to them? You know, I can only speak from a vendor’s perspective, but I know that the approval process in health care is nightmarish at best.

[00:11:43] Chris St John: The easy answer to that question is that you go to the vendor’s websites and you fill out a little form that says I’m interested, and they send the rep and you talk to them, or you go to the state and say, I wanna start a program, and they say, great. Here’s the pile of paperwork you have to get involved with. But I think what matters most is the interest and the passion to want to have it, and that’ll make you hungry for going through all the literature that was available at the time, like like I did to make sure that I knew what I was getting myself into, going around, and then literally door to door talking to the oncologists and neurologists and radiation oncologists and saying, you know, this is what I’d like to do. These are the outcomes that people are seeing if we select the patients appropriately. This is really exciting. What kind of patients do you have? This is the type of workup we need to do. I was really hands on when I started. I was making the phone calls to patient consults myself. I was booking them myself. But being intimately involved with developing it from the ground up now makes me, I think, a bit more prepared because I know what it’s like to have to talk to the insurance companies. And I understand the the revenue cycle, and that becomes important for a hospital system because they’re gonna lay out money for these therapies upfront. They’re not gonna get paid for a bit. And on some days when I’ve got five and six therapies, that’s a huge amount of money that I certainly didn’t appreciate at the time why the CFO was getting getting a bit nervous because money’s getting laid out. We’re not a 100% certain how the reimbursement’s gonna look early on, and they very appreciative that the system here was you know, kinda patient with what that process was. And I think a lot of that had to do with me presenting what a vision could look like for it. That this is not just gonna be a place where patients come, we inject, and they move on. You know, we’re gonna provide a full service care. You know, the oncologists, urologists, or the refers are know that when they send the patients to us, we’re gonna do our job to do the imaging up front, do the due diligence for clearing the patients. We’re not doing this just because we can. We have to get the right patients the therapies. And, you know, when I go back, we showed our fellow do this Last year, um, she went and looked at all of our patients and, you know, we kind of found that while half our patients never would have met criteria for some of the early drug trials, they were kinda too sick. The ones who did had just as good outcomes with us as they did at these big academic centers, and I think that, know, really kinda helped us. And so, look. We’ve got two patient populations in the community setting. We have the ones that are kinda teed up that fit the mold for these trials, and then we have others that are just quite sick. And we’re using these therapies from a palliative standpoint to patients that they’re feeling better so that there’s, I mean, it was anecdotally a reason to keep doing it. But, hey, we’re having those discussions and talking to the refers and saying, look. I know you expected this amount of life expectancy gain. You didn’t get it, but, you know, these are the patients you’re sending me. These are the ones that are in the trials that you’re getting your data from. They’re very discrepant. And I think going over some of those early outcomes with them certainly helped us grow as well because we could temper what the expectation’s supposed to be. But a lot of that was really just getting my hands on everything I could read so that I I could be the informed one, which the entire system didn’t have anybody like this before. So a lot of this was myself learning and then teaching anybody who would who would listen what this is and what’s entailed, and I think that’s what’s been helping us so far.

[00:14:39] James Cassuto: Yeah. And so I wanna push a little bit about the internal approval process just because I know every single facility, even if they’re within a larger IDN, is gonna have a different internal approval process. So it’s not like you can just give us a road map for anybody who wants to make a phone call, get some Plupic Do, and get a thermostics program together. But how would you advise someone about navigating those internal approvals? Right? Like, it’s such a piece of the puzzle that I think is so often missing from health care is how these facilities are actually working and what voices need to be involved.

[00:15:13] Chris St John: That’s a good question. I don’t know all the voices. I’d love to.

[00:15:16] James Cassuto: Right. I mean, that’s what I’m saying. No one knows.

[00:15:17] Chris St John: Through that process, you know, I guess from the physician side, getting the refers, getting the CMO, getting the the even the the CEO excited about what this could be for the hospital, I think, was the biggest thing I could do. I’ll bring a cheerleader for that. I presented at trustee meetings. I presented grand rounds. I presented to anyone who who I could on the clinical side of things to say, this is something we don’t have. This is something we need. And then once there was, I think, a lot of interest in wanting to pursue this, that’s where we got the CFO involved. When I spoke to the drug companies themselves, I put them in contact with our finance team, our authorization teams. And these companies have representatives reach one of those. So there’s ones I speak to from a product side and then a sales side, and then there’s representatives who come in and just talk to our billings team. So I wasn’t in all those discussions, but all of those were happening simultaneously. The biggest for us, I think, from a hurdle standpoint was really getting the radiation safety approvals, making sure that we had the drugs on the license. And from a practical standpoint, that’s not terribly difficult. We have a fantastic radiation safety officer who took ownership of that. From a state standpoint, I hope New Jersey yeah. Someone in New Jersey is listening. You guys are horrible. This is this was one of the longest and most arduous processes, and it didn’t have to be. I think there’s a ton that more we could be doing at this hospital that we kinda have to pump the brakes on a little bit just because the approvals at the state level take so long. I went on paternity leave, and, you know, it took seven months to get the other NUC med physician on the license, and that’s not a hospital problem. That was a state one. I don’t know if that’s in every state, but New Jersey, you guys gotta do better.

[00:16:50] James Cassuto: Yeah. I mean, I feel like that’s gotta be every state to some degree. But being from New Jersey, as I said, I also would like to suggest New Jersey to get your shit together. Excuse my language. So you were saying earlier, and this is something you talk about publicly, that every patient, every cancer is different. And so now that we are at this point where we can start to treat them that way, how does that start to change everything else going on internally with your program, workflow, staffing, mindset of the team? Right?

[00:17:21] Chris St John: Yeah. I guess I was quite fortunate that because I came, there was nothing, which means we could build it the exact way that we wanted to. Then I tried to keep it as fluid as I could knowing that we’re gonna find better ways to do things along the way, and then we had to have a way to to have easily adopt those into our workflow. At this point, we’ve been able to bring on a a nurse practitioner within the radiology department. We’re able to bring on a scheduler on one of our MOAs, but also happens to be a CMA and has clinical kind of workflow experience. And we have this giant spreadsheet that we’re able to detract the patients on. So we have someone who’s reviewing every single one of the labs every two weeks, making sure that the trends are where they need to be. We’re not seeing bone marrow suppression because the radiation toxicity. There’s a way for her to easily get in contact with me and and essentially say, look. This patient is not doing as well whether PSA is rising if they’re on a pluvicto for prostate cancer. So we have people now who are monitoring the labs and making and from a progress standpoint. We have someone at the front desk whose primary role is being the face of the program, talking to the patients, having a point person. I think people really appreciate having that consistency, which then frees me up to actually do the nuclear oncology part of all this, which is reviewing the scans with a fine tooth comb. Yeah. How many lesions of that are we seeing? What percentage of them are meeting certain thresholds? At least, you know, what for what we have right now in the literature that would suggest these are going to be lesions that are treated well with a certain drug. Is there a better one out there if I think someone’s a good candidate for a theragnostic treatment, but we don’t have the drug here, but there’s one in trials. I’m sending them there. I’m, you know, we’re trying to do our best to make sure that whatever we’re giving the patients, the best we can offer them. And the focus here a lot is is on how do you integrate imaging into selecting the patients, keeping them in the program. We image everybody after they get therapy. That’s not commonly done. About half the centers don’t do that. But we’ve seen that if enough of the lesions have been destroyed, then the next time I give you intravenous radiation therapy, it’s not gonna go anywhere. So can I put you on a bit of a holiday? We’ve got patients on a year break from getting radiation therapy. Their PSAs are stable. Their PET scans are stable. We can watch them. And then when they seem to progress again, we can restart them on therapy. And we’re not just saying the manufacturer says give this every six weeks and you’re done. If we can prolong the amount of time somebody’s not on the second and third blood chemotherapy agents with these horrible side effects, then we’re not just giving them longevity benefit. We’re giving them a bit more from a quality of life standpoint. And I think that if a lot of our patients, so maybe the prostate cancer patients who are a bit older in the first place, you know, they’re really appreciative of that. So, you know, it’s not just do I green light you for therapy. It’s while we’re giving you treatment, when’s the best time to give you this drug? How do I give you a chance to recover? How do I extend the amount of time where I don’t need to start considering other types of medications because you’re otherwise healthy enough to keep going?

[00:20:09] James Cassuto: Interesting. I wanna make sure I have my mind wrapped around that because that feels very cool. So can you just say more on, like, how you’re assessing this amount of time that you, like how do I even think about it? It’s not downtime, but, like, time in between treatment.

[00:20:25] Chris St John: Sure. So there’s the minimum requirements that that’s from a safety standpoint. We know that when we give intravenous radiation therapy, while these drugs are trying to localize the tumors, they’re they’re flowing through your bone marrow. They’re flowing through kidney, the lymphoid liver. All these organs are getting exposed to radiation therapy. If you’ve got a patient with a a large volume of bone metastasis and we localize radiation to it, all the normal surrounding marrow bone marrow is going to get exposed to some degree. So I know for sure two weeks after we give this drug, there’s gonna be a drop in their in their white count, their hemoglobin, their their platelets. Um, that’s an expected finding. So the time between therapies is on every six weeks for Provicta or VA based for Lutathera, and then Pardin is incorporating that aspect into it. By typically, I’m not gonna shorten the time between doses, but after every therapy, we’re bringing the patients back and we’re doing imaging. These drugs kinda have two kinds of radiation they’re admitting. The majority is this beta emitter for curing the cancer cells. There’s a gamma component that we can image on our SPECT equipment. So every patient gets scans, which means I can see exactly where the therapy went. I can see one that I can compare its distribution to prior scans. And if there comes a point where we’re seeing along the way that the lesions are getting bigger, they’re getting brighter, there’s more of them, patient clinically is doing worse. We can tell pretty quick and say, you know what? This therapy is not working for you the way we thought it was. We have to find you a drug that’s going to work, and we’ll stop treatment. If we didn’t do that imaging, I wouldn’t necessarily know this. A lot of patients, there are anti hormonal medications for prostate cancer. The tumor markers we would typically wanna use like a PSA, they’re not as high as they should be for the amount of tumor volume there is. And some of that is because the lesions are mutating and they’re not kinda producing as much. So when things become unreliable, I’ve gotta find some way to manage the patient. I’m not I can’t only give you a 120 gray per lesion. You got 50 lesions, and then I have no idea where it went. I think that’s irresponsible. So we’re using these images to guide therapy, but the flip side is if we’ve had some patients that give them two doses, and on the third dose, when they come in for imaging, I don’t see any more lesions anymore. When I say, great. The next time I give you a therapy, there’s a good chance it’s gonna circulate in the blood, go through the bone marrow, the kidneys, the liver, get excreted, bind to nothing, and all I did was give you radiation toxicities potentially and and wasted one of your approved doses from your insurance company. So for those patients, we’ll stop the therapy. We’ll give them what we call a radiation holiday. We’ll keep following them with labs. We’ll do intermittent PET scans. But the first sign we see that there’s a recurrence or a progression, we can restart therapy. But because, unfortunately, at least for now, these therapies aren’t cures, um, buying you quality of lifetime. If this didn’t exist, you’d be going on a second or third line chemotherapy, and they’ve got neuropathy and hair loss and vomiting, and these patients feel miserable. So if you’re gonna wind up possibly there anyway, but I can give you the amount of time you don’t have to be on it as a maximum, and I can decrease total amounts of cycles you might have to be on total. You’re gonna feel better. You’re gonna go back to your life. You’re gonna get a lot of your life back, and I think that’s for a standpoint, that’s the reason to do any of this is get these patients pain free, get them to their next birthday, the next Christmas, the wedding, whatever it is that I’m going vacation not feeling sick and miserable. And I’ve got a lot of patients coming back saying, like, you give me my husband his life back, and that could just mean he’s able to go back to work on his farm a bit more. I love hearing patients tell me, you know, I I overdid it over the weekend. I started building houses again. I haven’t done that as a volunteer for two years because I felt so good. But I think we can maximize that by doing these kinda intermittent doses.

[00:23:47] James Cassuto: So your program as well is doing something rare. I believe you were using a diagnostic probe from prostate cancer and applying it to high grade brain tumors. Where did that idea come from? What made you think it could work? And what have you learned so far about not just using these techniques for other cancers, but overall future of various cancer treatments?

[00:24:10] Chris St John: I I mean, a nuclear medicine kind of community started using these tumor specific pet tracers on patients. You kinda start seeing that things other than what they may have been initially designed to test for start popping up. So someone has a brain lesion, they have a meningioma that’s gonna pop up on the PSMA pets and the DOTATATE pets, like like reduced for neuroendocrine tumor. Other cancers, breast cancer sometimes pops up on it’s right on the neuroendocrine tumor PET scan. So we’re seeing other things that kinda pop up. And then what we’re learning is that because of that, there’s opportunities if there isn’t a drug available to possibly image or even treat those kinds of of lesions. And, I mean, one of them happened to be the high grade glioma is like glioblastoma multiforme, and it’s a very aggressive brain tumor. It was showing up on these PSMA PET scans. When we kinda look into a bit more and you’re doing the pathology on it, you’re realizing that these PSMA PET tracers are binding to the tumor specific endothelial cells of these high grade brain tumors. So they’re binding to the vasculature, which is very cool because it means it’s you don’t have to now get these traces to cross the blood brain barrier to do something. They’re localizing, um, to the tumor itself. So what we have in the neuro oncology space is that on MRI, some of these lesions can look very similar, once they’ve had all this radiation therapy and treatment to either a worsening disease picture or post treatment changes, radiation necrosis. And when you do the MRI, they become equivocal. You do them again in three months and three months and three months, and you follow them. And then some of these will get better. You say, great. That was radiation necrosis. Some of them get worse, and you go, well, this was real viable tumor that we maybe could have picked up months before. And for some of these patients, that’s a big deal because you could start them on new medication. The life expectancy might have been six months at that time point. So kind of what my proposal was to the hospital here is that, can we use this PSMA PET tracer, which in a couple case reports had been used previously. But, you know, how do you make this kind of a mainstream clinical tool for us? And did a couple patients had some path proven or pathology proven kinda positive for recurrence, and we’ve been able to build this now into our kinda regular care here within the center. So for neurosurgical patients from a brain tumor standpoint, if there’s MRI findings that are equivocal for disease recurrence or worsening disease versus a radiation necrosis, we have these pet tracers available. We have grants to kinda support the funding for it. It’s off label, and we’ll image the patients with a PET scan. We’ll then fuse it on one of our computers to the MRI, and and we’re giving the surgeons a new road map for how to, you know, which part of these lesions are are viable and which aren’t. I’ve got pictures where before they were referred here, there was a biopsy done, and you can see where the needle was placed in the brain tumor. We do the PET scan, and you got, like, a horseshoe picture of viable tumor, and the needle’s right in the middle where there’s nothing. And you think, well, had we had these types of pictures beforehand, you would have known exactly where to target to prove that this was viable. And and that’s now been kind of a part of our program. And we’re using that for brain tumors. The neuroendocrine tracers we’ve been using for meningiomas, we’ve been using them for especially based on skull meningiomas, which are very difficult to operate on with the idea being and, similarly, if I can show that we’re getting enough of the tracer to these sites, then we can treat them. And then there are trials now using the Lutathera to treat basis scum and the geomas. We used one last year to treat a very aggressive basis skull paraganglioma that had eroded through the bone, was pushing on the patient’s brainstem, not operable candidate, and not responding to anything, kinda came to us as the last ditch kinda effort to help him, and we did what we typically do. We brought him in, did the imaging, calculated what kind of dose we thought would go to these lesions, shrunk the tumor enough, headaches went away, swallowing got better, patient was kind of in a in a better position because of this. But when you think about where the future this is going is, it’s nice to have the new tracers for new cancers. One specifically for ER positive breast cancer, one specifically for triple negative breast cancer, sarcomas or colon cancer. And they’re gonna have, at one some point, their own specific pet tracer, which then we’re gonna label with the radioactivity for therapy and have kind of a thermostics pair. But it’s nice if there’s some crosstalk between them so that while we’re while we’re waiting, we have something to offer patients.

[00:28:07] James Cassuto: Yeah. For sure. I wanna ask you at the beginning of that response, you were touching on something to do with the vasculature and how it ties in. I believe I could be wrong. Correct me if I’m wrong. But wasn’t a lot of your early training and research specifically on vascular physiology to some degree? Yeah.

[00:28:24] Chris St John: That’s what the PhD is, and it’s all vascular physiology.

[00:28:27] James Cassuto: So did that come into play when figuring all this out to some degree? Like, did you kind of have a bunch of this in your back pocket already?

[00:28:34] Chris St John: Yes. I had the mechanisms in the back pocket for sure. And when I was doing kinda early experiments, a lot of it was focused on we were looking at inflammatory imaging and diabetes, and can we label vascular troposcopy components with these kind of probes? And that’s always kinda stuck with me, certainly for the brain tumors, because all the the difficulty we have in getting drugs to them is that you’ve gotta have to cross this blood brain barrier. But if you can identify vascular targets and park your radiation there, some some of these radioactive molecules will travel two and three millimeters across a 200 micron blood brain barrier. I don’t have to cross it. I just gotta get it close and dump the radiation on the other side of it. And it certainly helps seeing kind of in real time when I was doing the research what the binding rates were for some of these probes. And at that time, we were looking, how do we deliver MS type drugs to there? But it doesn’t really matter whether the payload is for MS or it’s radiation for tumors. The idea is the same. You know? Can you use the vasculature as your conduit and even as your target for therapies? And instead of going to the tumor, certainly for things like GBM or these other very aggressive tumors, if they’re poorly differentiated and they’ve kind of a lot of the mutations, you might not have a specific target on the surface to go after. But you have the blood vessels feeding them, and those blood vessels are typically a bit different than the normal ones in the body. And and now we have these integrin kind of binding prognostics pairs, which are doing just that. You know, can you target the tumor specific microvasculature to put your radiation therapy or your antivascular medications to kill the tumors?

[00:29:59] James Cassuto: So looking at the next five, ten years ahead, what radio tracers, therapies, cancers do you believe are gonna be defining the next chapter of theranostics?

[00:30:08] Chris St John: Sure. So I think there’s two things we have to focus on. One is the type of radiation that we’re going to be using to pair for these nuclear thermostatic agents, and the other is the tracers themselves. So from a radiation therapy standpoint, a lot of what we’re using now are the tissue one seven seven and nutrient 90 kinda isotopes. Those produce beta emissions that it’s predictable at least for now, but one of the issues we’re having with these types of treatments in general is that they’re a lot of reliant on kind of high oxygen content in these tumor microenvironments. We’re gonna make free radicals. We’re gonna make superoxide with the radiation attacking those specific elements, and that’s what’s gonna be then used to destroy the cells. We’re looking at a lot of single strand DNA breaks with beta emitters, which is nice, but I need double stranded breaks to kill cancer cells. So I think as this moves forward, we’re gonna see things like the actiniums, actiniums, these alpha emitters. So bigger, heavier molecules that will deliver much more energy over a shorter period. So what you’re gonna wind up having is a much higher kill rate for the same amount of radiation that’s produced. And we’re seeing this now in trials where someone with a lutetium one seven seven PSMA, that’s Pluvicto, therapy, you know, did well, um, had a recurrence in a couple months. Afterwards, was put on the Actinium therapy, which is an alpha emitter, essentially, of a radiologic remission, which is incredible. One of the challenges is generating enough of these therapies in a cost effective manner. But you’ve got companies kind of all over the world really looking at and trying to tackle this because I think that’s going to be an an incredible gain for us. And then the other is the tracers themselves. So right now, the tutoring therapies are Pluvicto and Lutathera. They’re targeting very specific, well differentiated tumor markers. But you have the triple negative breast cancers. You have pancreatic cancer and ovarian colon that don’t have a marker. And as if you had many, they might not have a specific tumor marker if they wanted being exceptionally aggressive. So you have things like FAPI, which are targeting tumor microenvironment fibroblasts, and cell populations that are kind of a high density in those environments. And from a radiation standpoint, that’s great. If I can get it close enough to the tumor, we can kill the tumor with the radiation therapy. So those new targets, I think, are what’s going to make this even bigger than what it is to the point where I think you’re gonna wind up having nuclear oncology as a burgeoning specialty with the nuclear medicine where you have kind of asked some experts in the imaging and treatment of cancers with these therapies alongside your radiation oncologists, your medical oncologists, surgical oncologists, just because there’s so many cancers that are gonna be touched by this. I think there’s a part of the Europe that said and I forget the, you know, years in the future, but something like sixty five percent of all cancers are going to have a theranostics pair that can be used in treating them.

[00:32:47] James Cassuto: Okay. So for health systems or radiology groups, like, you know, somebody wants a piece of this pie. If someone wants to build their own program, they don’t know where to start. In terms of, like, a few small actionable steps, you know, wake up tomorrow morning, what should they do?

[00:33:02] Chris St John: I would go to the Nuclear Medicine Society’s website, especially this morning, in preparation for this question. They’ve got incredible resources, you know, what’s required, what kind of teams are required, what does the landscape look like, and that’ll get you an idea of the type of personnel you should have available to deliver the type of care that that you want. I would talk to the vendors that are manufacturing these therapies, and they have a vested interest in your success too. That’s how they’re gonna get the pipeline in. And they’ve got teams in place to help you get your billing set up, get ordering set up. You’re gonna have to talk to your radiation safety officers and and, you know, get these drugs on the state light on your license. That’s kind of the bare minimum that that you have to do just to get these things approved and through. And and I think if you can get all that, then while you’re waiting for your state to approve this over the next six months, that’s when you gotta start talking to your refers and building a relationship with them, talking to your radiation oncologists that are there. They might be interested in in helping from a dosimetry stamp, but they might even be the ones doing this. They’ve got so much, you know, kind of background in in nuclear radiology anyway or nuclear, um, physiology anyway. A lot of centers are turning to them, but I think that’s where I would start first. And then the other is go to the Theragostics conferences. And you’re gonna meet people like myself, other other thought leaders, and you’re gonna gain kind of the clinical insight that you’re not gonna see in reading the manuscript, or how do you go into handle the patient when all of a sudden they’ve, uh, they’re not feeling where they wanna go to the emergency room a day after you just gave them very high doses radiation therapy, and you don’t wanna contaminate the entire department and those kind of practical but necessary, uh, kind of scenarios and questions are gonna come up.

[00:34:32] James Cassuto: Awesome. Well, I think that is all the time that we have today. James, do you have anything you wanna plug or anything that you wanna, like, drive people to in addition to the resources that you just gave us?

[00:34:44] Chris St John: I think that because Theragnostics is so rapidly evolving and you’ve got so many either new centers popping up or centers in the area that are kinda doing their best to provide kind of this necessary service, I think from a patient standpoint, it’s kinda nice to know that there are differences in how these are delivered. From our standpoint here, where we’re doing our best to do a lot of monitoring of blood work, do monitoring with imaging. And then we’re really trying to make you know, give our community here kinda academic level care. I think there’s a lot of and I know this this was just published too. There’s a lot of variability in how care is delivered. So I think from the patient’s standpoint, when you’re undergoing these therapies and you’re talking to your providers, you ask them, how are you gonna monitor the progress? You’re gonna do imaging more than just blood work. You have the ability to do intermittent dosing. And it’s not that they’re necessarily difficult. That’s just another thing that your provider’s gonna have to learn in Poland, but I think that that’s what’s going to get you the best outcomes, and I think that’s important.

[00:35:34] James Cassuto: Well, James, thank you so much for joining us today on Rethink Imaging. Doctor James Casuto is the director of nuclear medicine at Overlook Medical Center and assistant associate medical director of nuclear medicine for Atlantic Medical Group. James, thank you so much for joining us today. I hope to have you back sometime.

[00:35:50] Chris St John: I appreciate it. Thank you. Likewise.

[00:35:52] James Cassuto: Alright. Thank you. Frame by Frame, Rethink Imaging is brought to you by Imalogix. Here, you’ll find engaging interviews with thought leaders, experts, and patients sharing stories that showcase the transformative power of medical imaging. To discover how Imologix is rethinking imaging in health care, visit imologix.com. Be sure to subscribe to Frame by Frame Rethink Imaging on Apple podcasts, Spotify, or wherever you listen. And from all of us here at Emalogics, thanks for tuning in.

Questions from This Episode

What is theranostics?
Theranostics pairs diagnosis and treatment around the same molecular target. If imaging shows a cancer expresses a specific receptor or protein, a therapy can be directed to that same target. Dr. Cassuto describes it as imaging moving beyond diagnosis and into treatment.
How does imaging guide theranostic treatment decisions?
Imaging informs who should receive therapy, when treatment should pause, and when to change course. Cassuto’s team uses post-therapy imaging to confirm whether a treatment is working, which supports therapy holidays, reduces unnecessary cycles, and helps patients feel better for longer.
Can a community hospital run a theranostics program?
Yes. Cassuto built one at Overlook Medical Center that mirrors academic-quality care without making patients travel. Getting there involves internal approvals, radiation safety planning, staffing, workflow design, and financial considerations, along with imaging expertise to select and monitor patients.