Cerianna: Advancing Estrogen Receptor Targeted PET-CT for Breast Cancer Diagnosis and Beyond

You so much to the nurse navigators in the audience for the opportunity to be here to discuss estrogen receptor targeted pet CT with Seriana. And how to best identify patients with recurrent and metastatic breast cancer that can benefit from this recently FDA approved technology. I'll start with my disclosures, and I also disclose that I like to teach molecular imaging starting at an early age. This is my son, Ilia, and my daughter, Annabelle, that have helped me teach numerous courses on molecular imaging and therapy. This was, of course, before the COVID era. So I provide you with a more updated picture of the family so you can see how they are well adapting to our move from from New York to Southern California. These are disclaimers. Most importantly, the information communicated in this presentation is intended at good faith. To be truthful and non misleading and presented with fair balance. And please do not copy or share without express permission, Zyanexa, or GE. Serriana is a radioactive diagnostic agent intended for use with positron emission tomography, for the detection of estrogen receptor positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer, and that in clinical trials, side effects were very rare and included a less than one percent rate of injection site pain and alterations in the sensation of taste. This is the mechanism of how this technology works. I am someone who specializes in molecular imaging and therapy. And this is how I like to explain how molecular imaging works. As a a key fitting into a lock. For each different type of cancer cell, that cancer expresses targets. Either on the surface of the cell or within the cell that we can specifically identify. And build binding agents that hit that target like a key fitting into a lock, so that we're able to find that target specifically, which gives us good sensitivity in detecting lesions, and we don't detect other types of things that that we're not looking for. We take that binding agent, and we link to it something that is radioactive, known as a radio isotope. If the radio isotope emits low level radiation, such as fluorine eighteen that we will discuss today, That builds us a key that hits our target and allows us to image that target in a machine called a pet scanner or POSatron emission tomography scanner. If we take off that radio isotope, that emits a low amount of radiation and replace it with something that emits a very high amount of radiation Now we have built a key that can bind to the specific target on a cancer cell and emit an amount of radiation that can kill adjacent cancer cells, and now we have developed a molecular therapy specific to that tumor tank. For today, we're gonna use this model and talk about the specific agent, Seriana. Which is an estrogen receptor targeted imaging agent. The cancer cell that we're talking about, of course, is breast cancer, the target is the estrogen receptor, which exists within the breast cancer cell and is over breast and about eighty percent of breast cancer patients. The binding agent that we use is estrogen or estradiol, This is physiologically available within all of our bodies already, but we take this estrogen and we link to it a radioisotope known as fluorine eighteen. Florine eighteen emits a positron that we can detect in a pet scanner. And now we have a radio labeled estrogen that acts like a key, hitting our target, the estrogen receptor, and allowing us to visualize breast cancer cells throughout the entire body in a noninvasive way, Now let's talk about some of the potential applications of utilizing this estrogen receptor targeted imaging. In order to help you identify the patients that may be most appropriate to benefit from this agent. The first and most foremost, I believe is going to be to detect the estrogen receptor status in recurrent or metastatic lesions. Let me show a few examples of this. This is a patient with known estrogen receptor positive metastatic breast cancer. So the patient's pathology has been stained, immunohistochemistry has been performed, and it has been determined that this patient's tumor is estrogen receptor positive. So they were placed on estrogen receptor targeted therapy. First line estrogen receptor targeted therapy. Unfortunately, the patient began to progress And the question for this patient, which is extremely important, is whether we should because we know we need to change therapy. Do we change the therapy to a second line estrogen receptor targeted therapy? You could try a second line estrogen receptor targeted therapy that the patient would be on for several weeks or months in order to see if the patient responded And then if it didn't work, then you used another line of therapy. This is where Seriana may have its greatest role. We perform a Serriana pet scan in this patient when they progress at the time when they progress on first line estrogen receptor targeted therapy. Here is a maximum intensity projection or mip image of a sariana pet. In this patient, we can see the normal physiologic structures. This is the liver, as the Serion is excreted normally through the liver, we'll see the biliary tree into the bowel And we may also see some kidney, ureter, or bladder, as to a lesser extent, the agent is excreted also through the urine. But what we don't see are these multiple sclerotic osseous lesions, which represent the known site of the patient's disease. We do not see any uptake within the spine. Here is the fused CT with the Serionna pet. There's no uptake in these lesions. Now, that does not mean that the disease is not present. We know the disease is present. There have been other studies that tell us that the disease is progressing. It's getting worse. However, this study tells us that the estrogen receptor in these tumors is not available to be bound by our estrogen receptor targeting agent, Seriana. Traditionally, imaging in oncology has been used during therapy to determine if the tumor is getting smaller or bigger, and that helps us determine if we should continue on our therapy or select something else. But that's done after the therapy has already been performed. The Serrianna pet can be performed before you start a new line of therapy, this is a similar scenario where the patient has known estrogen receptor positive metastatic breast cancer. So the breast cancer, again, is estrogen receptor positive on pathology. They are unfortunately progressing on first line estrogen receptor targeted therapy. In this case, there is an FDG pet, which is telling us that the disease is unfortunately progression. There are multiple areas of bone and liver that demonstrate the FDG of it to be telling us that patient has active disease, and the active disease was getting worse compared to a prior study. This patient undergoes a fluorine eighteen fluoristradiol, PetScan, which is the Seriana PetScan. Right? We said this is radio labeled estrogen, the f eighteen Floristradiol pet. The fluorescent dial pet fails to demonstrate these lesions. Now that does not mean that these lesions are not present These lesions are present. But these lesions do not have estrogen receptor that is accessible to Serrianna. Now, I use this slide in particular to demonstrate something that is very important. These two pictures are obviously very different. We see the brain on the FPG pet. We see the liver and the bowel more on the pleuralastradiol. That's because even though both of these studies are called pet scans. They are truly entirely different scans. And people are gonna have to get used to this. When people say, let's order a pet, they're usually referring to FD pet. FDG is a molecule that is radio labeled sugar. So it goes wherever the sugar goes, and tumors like to eat sugar in order to provide their metabolism. So we can see tumors on an FDG pet scan. The FES Pet scan or the Serriana pet scan is not going to see all tumors. It's only going to see the tumors that have estrogen receptor. So these are two very different scans. They're being done for two very different purposes. The FPG PECScan is being done to assess how much disease is in the body And then the FES PetScan is being performed to determine if that disease has estrogen receptor So people I think are gonna have to get used to instead of saying, let's order a pet scan. They're gonna have to start saying, let's get an FDG pet scan to evaluate the extent of disease. Or let's get a Serriana pet scan, be wary that in the future as more and more of these pet agents become FDA approved, you might accidentally order the wrong pet scan. I've seen this already performed in practice where we wanted one type of pet scan, but an FDG pet was accidentally performed instead because most people default to thinking that the FDG pet scan is the only pet scan that's out there. Now, let's talk about the reverse of those last two patients. Again, this patient is estrogen receptor positive metastatic breast cancer, and is progressing on a line of estrogen receptor targeted therapy. The CT scan demonstrated that these lung metastatic sees are progressing. The Serrianna PetScan is performed and demonstrates that these lesions are avid for Serrianna. Let's look at a complicated case, an example of this comparison between metabolic imaging with FTG pet and estrogen receptor targeted imaging with Seriana. This patient, again, has an estrogen receptor positive metastatic breast cancer. They're progressing on their current course of disease. Their FDG pet scan demonstrates states that there are multiple multiple sites of FDG avid disease, unfortunately, in this patient suffering from metastatic breast cancer. This shows us two different types of lesions. One of those lesions is not avid, for Serriana. So this lesion apparently doesn't take up the tracer. Here is a different osseous lesion that does take up the Sariana, although it doesn't take up the FDG. I'm gonna show that more specifically on our cross section images of this patient. Remember that often the right side of the image is the left, and the left side of the image is the right, so we're looking at a lesion here in the left ilium, and another lesion here in the right ilium. The lesion in the left ilium is avid for Serriana, but is not avid for FDG. This lesion is then biopsied, and the biopsy shows us that this lesion expresses the estrogen receptor. However, the majority of lesions are like this lesion in the right ilium. It is avid for FDG, but it is not avid for the fluorester dial. This lesion was also biopsied. This lesion demonstrates that it is negative for estrogen receptor. So this patient has two different types of breast cancer clones, at least. And it's important to realize that there is a greater and greater recognition that breast cancers may change their estrogen receptor status from the initial site to metastases, and metastases may differ from each other. Therefore, not all treatments are going to be successful at treating all the metastases in an individual patient. If we go back to that overview whole body imaging, We can see that the majority of the lesions are not Serriana avid. Only a few of them are. So most lesions are like this lesion and only a few lesions are like this lesion. Now we have information from these two bone marrow biopsies. But obviously, biopsies hurt They require a needle to be stuck in through the skin into the bone. And also, they only provide information on a single site at a time. Whereas, the Seriana pet is able to provide a whole body evaluation noninvasively of the estrogen receptor status. These two biopsies tell you, Some lesions are positive. Some lesions are negative, but we don't know the proportions. The Serrianna pet, it evaluates the entire body and tells you most lesions are like this. I think we've seen this in practice now. Here's a recent manuscript with recent estrogen receptor targeted therapy including an AI and a CDK four six inhibitor. Okay? And again, two patients from this study, one has disease shown, I should say, they both have disease shown on FTG pet. So, both patients have disease. The FES are performed in both patients. In the top row, the Seriana lesions are avid for Seriana. Well, the lesions are avid for something that finds the estrogen receptor, and after estrogen receptor targeted therapy, A repeat FDG Pest scan demonstrates that the majority of lesions indeed have been treated. This patient responded well to treatment. Let's look down at the bottom, FEDG avid tumor. The patient predominantly is not avid for Seriani. There are a few lesions, but the majority of lesions are not avid, the estrogen receptor is not accessible. All patients in this trial did receive therapy. This patient did not respond to estrogen receptor targeted therapy. The disease either stayed the same or even may have slightly progressed. We can use the Seriana pet in patients with known progressing disease. So that is my first of the most important potential applications for estrogen receptor targeted imaging with Seriana Pet. I will more quickly go through potential applications two, three, and four. Potential application number two, is to assess estrogen receptor status and lesions that may be difficult or impossible to biopsy. This is a patient who had an estrogen receptor positive breast malignancy and developed a lesion in the brain on MR. And the question being, is this a estrogen receptor positive breast cancer metastasis is well answered by performing an FES Pet scan, which is avid, demonstrating that this lesion does have estrogen receptors in this lesion, this is an estrogen receptor positive metastasis from breast cancer. This is another important point of distinction between FES and FDG. FDG, the sugar agent with is the more common pet scan, the FTG pet is not specific for tumors. You can see not only tumors that take up the sugar, but also inflammation or infections that take up the sugar, and often there are false positives on the FTG pet. The FES pet is more targeted targeted to the estrogen receptor. So if this was something like an infection or inflammation or radiation necrosis, it would not express estrogen receptor, and it would not be seen on FES Pet. So, if you didn't have Serriana Pet, What you would have to do in order to assess if you wanted to assess this lesion is sample the tissue. Obviously, that could be a difficult procedure So, the noninvasive FES PET scan is a very good application for assessing lesions that you may not wish to assess by biopsy. Potential application number three. You can use Seriana Pet to help provide you additional information when other studies are inconclusive. This is a manuscript that was performed on one hundred patients in which we'll call standard of care imaging, or more common imaging such as bone scan or CT was equivocal for whether disease did or did not exist. This patient had a bone scan with a few mild bone scan foci. And the question is is this degenerative change and maybe fracture in a rib, or does this represent true metastatic disease? Important to distinguish those two possibilities on the bone scan. The Seriana PetScan performed in this patient demonstrates that these sites are FES avid, they express accessible estrogen receptor. Degenerative changes don't express estrogen receptor. Fractures don't express estrogen receptor. So this more specifically identifies for us, this is a, aseous metastasis, in a more conclusive way than the bone scan does. And in this trial, more than eighty five percent of patients that were equivocal on bone scan or CT or other imaging methods the application of Serriana or FES Pet was able to solve the clinical dilemma. Finally, I hope there'll be a growing application at FBS Pet to help assess the extent of disease, particularly in breast cancers that are not very metabolically active and, therefore, are not well seen on FTG pet. Here is an example. A patient with The primary tumor was estrogen receptor positive globular breast cancer. The patient was previously treated. There was suspicion for a left chest wall recurrence on FTG pet. Here's that suspicious lesion. There's one focus in the chest wall, which was suspicious for recurrent malignancy. Now this could be biopsied, and you can prove indeed there is this one of disease. But this does not or did not accurately evaluate the extent of disease in this patient. Look at the FES or Seriana PetScan on this patient, which an unfortunately demonstrated numerous ostias as well as soft tissue lesions throughout the body. This patient suffered from widespread metastatic disease, and we could be potentially under treating if we thought there was only one lesion in the chest wall. So, the Serriana pet scan was better able to depict the extent of disease than the FTG pet Keep in mind this patient was a lobular breast cancer patient. We'll talk about that more in just a moment. But here's one more case example before I discuss lobular breast cancer specifically. This patient had a estrogen receptor positive lobular breast cancer and they were suspicious for disease recurrence because disease markers were increasing tumor markers were increasing. And FDG pet the more common pet scan was performed, and they found FDG avidity in lung lesions. They said this must be the site of disease, so they biopsy the lung. This came back as benign granulomatous inflammation. Again, FTG pet is not specific for malignancy. Many things can be FTG avid, especially infections and inflammation, such as this lesion. After the biopsy of the lung lesion, showed that this was benign, a Serriana targeted pet scan was performed. And indeed, the lung lesion is negative on the Serriana pet because inflammation doesn't express estrogen receptors. Unfortunately, the Seriana Pet demonstrated multiple sites of nodal, bowel, bone, and peritoneal malignancy, which was then biopsy proven to show that this was the site's of her recurrent disease. The Seriana pet was more accurate for determining disease extent than the FDG pet in this patient, and even the FDG pet led to a biopsy, which was benign because of something that was false positive on the FPG bet. I have one more case example. Just to demonstrate, in a patient we've had a CT and a bone scan. Here's our CT scan. Here's our bone scan. That had equivocal lesions. Here's sclerosis on the CT nearer to some degenerative changes, and some mild divinity on the phone scan. The question becomes, is this a malignancy that needs to be treated Or is this just degenerative change? Here, a floor or estradiol pet, the Seriana pet was performed, demonstrating that this lesion was not estrogen receptor positive. And almost certainly, this lesion is benign degenerative change, as degenerative change does not express estrogen receptor when metastasis would be expected, in most cases, to express. So all three of those case examples were done in patients with labular breast cancer. And there is growing recognition that labular breast cancer is different from the more common invasive ductal malignancy. So just like in pet scans, where we have to distinguish, hey, this is an FDG pet scan. It's looking at metabolism. This is an FES pet scan. It's looking at estrogen receptor, and there are other types of pet scans like dotatate pet scans for neuroendocrine tumors, PSMA, pet scans for prostate cancer, and a growing number of tracers that we'll be using on pet. It's also important to recognize that not all breast cancers are the same. The most common histology of breast cancer is ductal malignancy, which accounts for about eighty percent of breast cancers. The second most common is lobular breast cancer, which represents about fifteen percent of the remaining. And then the other five percent, there are others such as mucinist, papillary or other types of breast cancers, and not all breast cancers are just breast cancer. Robular breast cancer is unique in that it is known to have a loss of a gene called c d h one. Which encodes for a protein called e cat hearing. The job of e cat hearing is it's a cell adhesion molecule, so it holds things together. When you lose that cell adhesion, the tumors start to grow separately and apart. So, ductal breast malignancies tend to grow tightly packed in little balls, while labular breast cancer tend to grow in sheets and lines. More spread out less dense, and there are fewer cancer cells per unit volume than in ductal malignancies. You can imagine if there are fewer cells present, it makes those cells harder to find. And indeed, labular breast cancers are more difficult to detect on mammography, ultrasound, MR and FTG pet then the more common ductal malignancies. So lobularies are sneaky, they hide, they grow without detection And when they are detected, they're often larger than you may think they are because of its difficult to see the tumor and its extent. However, another additional thing to note about globular cancers is that they're estrogen receptor positive. Therefore, estrogen receptor imaging has potential in detecting this sneaky type of breast cancer that may not be able to be on other types of imaging. We published retrospective data, data that obviously needs to be confirmed in prospective studies, which are ongoing, that when you take patients with a labular breast cancer, metastatic labular breast cancer, and imaging in these patients, the Seriana pet, the estrogen receptor targeted pet can define lesions and how many lesions are present In some patients, you can bind lesions on the Serriana pet when no lesions are available on the FPG. So it is a growing area of using Seriana Pet to help assess the extent of disease in patients where the tumors may not be particularly metabolically active, such as lobular breast cancers and may be identified. By estrogen receptor targeted imaging. So here's my summary. Please keep in mind that molecular imaging is a really important advancement for patients with cancer. This is gonna be a growing area of radiology and medical oncology well into the future. There are molecular imaging studies to help patients with neur endocrine tumors, prostate cancer, breast cancer, and this is likely to grow. The number of cancers that can benefit from this in the near future. In particular, for this talk, we're talking about molecular imaging of the estrogen receptor. Performing estrogen receptor targeted imaging with Seriana PetScan. This is an FDA approved diagnostic a tool for the assessment of patients with breast cancer. And here are four potential applications of this estrogen receptor targeted imaging Sariana that we discussed today. First and foremost, to detect estrogen receptor status in recurrent or metastatic lesions as an adjunct to biopsy. This is my favorite application. This is expanding the the abilities of radiology. Instead of just determining if tumors are getting bigger or smaller, Second, we can help assess the estrogen receptor status in lesions that may be difficult or impossible to biopsy such as brain metastases. Third, you can detect estrogen receptor status in disease in patients that had inconclusive results on other imaging studies, this can help you determine whether cancer is or is not present. And then finally, I hope there will be a growing role for estrogen receptor targeted imaging for determining extent of disease, particularly in patients where the FPG pet doesn't do as well, such as in low metabolic tumors like invasive globular carcinoma. With all of that information, I will now thank you for your attention. I hope that this will help you identify patients that can benefit from Seriana Pet scans, my name again is doctor Gary Lainner from the Ho Family Cancer Institute in Southern California? Important safety information, indicates in usage. Sirion is indicated for use in the POSatron emission tomography, pet imaging for the detection of estrogen receptor positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer. Limitations of use. Tissue biopsies should be used to confirm recurrence of breast cancer and to verify status by pathology. Sierraana is not useful for imaging other receptors, such as human epidural growth factor receptor two per two, and the progesterone receptor PR. Contraindications, none. WARNING and precautions, risk of misdiagnosis, inadequate tumor characterization and other positive pathology. Breast cancer may be heterogeneous within patients and across time. Siriana images and is not useful in imaging other receptors such as HER2 and PR. The uptake of fluoroaster dial f eighteen is not specific for breast cancer, and may occur in a variety of positive tumors that arise outside the breast, including the uterus and ovaries. Do not use Serianna in lieu of biopsy when biopsies indicated in patients with recurrent metastatic breast cancer. False negative serrionous scan. A negative serrionous scan does not rule out positive breast cancer. Pathology or clinical characteristics that's justipation may benefit systematic hormone therapy should take precedence over a discordant negative Seriana scan. Radiation risks, diagnostic radiopharmaceuticals, including cerionic, exposed patients to radiation. Radiation exposure is associated with dose dependent, increased risk of cancer. Ensure safe drug handling and patient preparation procedures, including adequate hydration and voiding to protect patients and healthcare providers from unintentional radiation exposure. Pregnancy status. Assessment of pregnancy status is recommended in females of reproductive potential before administering Seriana. Adverse reactions. In clinical trials of an N of one thousand two hundred and seven, the most common adverse reaction seen occurred at a rate of less than one percent or injection site pain, the nausea. Use in specific populations, pregnancy, risk summary. All radiopharmaceuticals including its Ariana had the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. Advise a pregnant woman with a potential risk of fetal exposure to radiation from the administration of Seriana. There's no available data on Seriana use in pregnant women. No animal reproduction studies using florestragile AF-eighteen have been conducted to evaluate its effect on female reproduction and embryo field development. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U. S. General population, the estimated background risk of major birth defects and miscarriage and clinically recognized pregnancies is two percent to four percent and fifteen percent to twenty percent respectively. Lactation risk summary, there's no data on the presence of fluoroastral F18 in human milk, or its effects on the breastfed, infant, or milk production. Lactation studies have not been conducted in animals. Advise lactating women to avoid breastfeeding for four hours after Serion administration in order to minimize radiation exposure to breastfed and infant. Pediatric use, the safety and effectiveness of Seriana and pediatric patients has not been established. Jiatric use. Clinical studies of fluoresce or dial F-eighteen injections did not reveal any difference in pharmacokinetics or biode distribution in patients aged sixty five and over. Drug interactions, systematic endocrine therapies that target estrogen receptors. Certain classes of systematic endocrine therapies including modulators and down regulators, block reduce the uptake of fluoresce or dial f eighteen, and may reduce detection of positive lesions after administration of Seriana. Drugs from these classes such as tamoxifen and Flow of restaurants may block for up to eight and twenty four weeks respectively. Do not delay indicated therapy in order to administer Seriana. Administrative Seriana prior to starting systemic entrochem therapies that block ER. To report suspected adverse reactions, contact Xyanax, the U. S. Corp, a GE healthcare company at one-eight forty four nine four six six three nine two or FDA at one eight hundred FDA one zero eight eight or f t a dot govmedwatch. For information related to Seriana, please email your inquiries to medical affairs at zyanexa dot com. Thank you for your participation in this event and your interest in Seriana.