Targeted Radionuclide Therapy Moves Earlier Across the Cancer Treatment Continuum

Clinical Summary:

• Dr Tagawa discusses targeted radionuclide therapy and theranostics in oncology, focusing on tumor-specific delivery of therapeutic radioisotopes and diagnostic imaging to identify appropriate patients for treatment.

• Lutetium-based therapies and radium-223 are being explored earlier in the treatment continuum, including emerging frontline applications. Treatment requires multidisciplinary coordination and attention to supportive care, radiation safety, and post-treatment monitoring.

• Theranostics offers an approach to guide patient selection and deliver targeted radiation. Collaboration among medical oncologists, radiation oncologists, and nuclear medicine specialists is essential to integrating these therapies into clinical care.

Scott Tagawa, MD, Weill Cornell Medicine, New York, New York, discusses the evolving role of targeted radionuclide therapy and theranostics in oncology, including how diagnostic imaging can help identify patients most likely to benefit from treatment.

Dr Tagawa reviews how these therapies deliver radiation to tumor-specific targets and discusses the use of lutetium-based therapies and radium-223 earlier in the treatment continuum, including emerging frontline applications. He also highlights the importance of multidisciplinary collaboration and practical considerations for supportive care, radiation safety, and post-treatment monitoring.

Transcript: 

Hi, my name is Scott Tagawa, I'm coming off the hot topic in the plenary session at the Great Debates in New York, talking about targeted radionuclide therapy. 

In terms of terminology, targeted radionuclide therapy implies that there's some sort of therapeutic radionuclide—today, mostly beta-emitting, but it also could be alpha-emitting, and there's a future for Auger and electrons—with some target, which is usually a tumor but also could be stroma, with some therapeutic intent. What we have in the world today are some that lead to progression advantages, some that lead to symptomatic advantages, and some that lead to overall survival advantages. But we now have a number of different diseases, a number of different targets, and a number of different drugs that were discussed today.

I'd say, at a high level, this really started with thyroid cancer and looking at iodine-131, both in terms of imaging with iodine-131 or 123 in terms of PET, as well as treatment with therapeutic intent using iodine-131. And that actually leads to cures much of the time. So that really set the stage, both in terms of a therapeutic drug against a target that is known to be present most of the time, but also the ability to look at the target.

In terms of what we feel is the field of theranostics, which is “see what you treat,” that is something that is out there for most of the settings where we do some sort of imaging. This helps us select individual tumors/patients for one of these therapies. Sometimes these therapies are administered when there are no other choices. But most of these are now moving up in terms of lines of therapy, and several of them are used at the diagnosis of metastatic disease or even in the adjuvant setting when it comes to iodine-131. So that's kind of a broad view.

For the physician who has a patient sitting in front of him or her with a disease that has one of these indications, one of the things that is a little bit different is that we need to be mindful of ordering these imaging agents. That's how we select the patients and tumors. Sometimes it's with an image that is kind of inherent and may happen all the time, such as a bone scan looking at radium-223 and hydroxyapatite, as well as a CT scan or MRI—cross-sectional imaging to negatively select, i.e., no visceral metastasis or big lymph nodes.

There are other times, in the field of prostate cancer, when we're using PSMA PET. We're using that for initial staging, for assessment of localization for biochemical recurrence, or in the study of known metastatic disease, assessing for the target. But one of the things that we need to do as the primary people taking care of these patients is to order the PSMA PET. We can get help from our radiology or nuclear medicine colleagues in terms of exactly which agents, but it is a test that we need to order to help select the patients.

It's very much akin to doing next-generation sequencing, looking for a genomic target, or immunohistochemistry, looking for a protein target—something that we need to order to then look for some additional information about therapy. But that is something that is part of the field of theranostics in terms of the imaging, and that's, you know, one of the main ways that we select the agents.

These are agents that are radioactive and are administered by an authorized user. Generally speaking, what I call the primary care providers for these patients, who are hematologist-oncologists or, in some cases, surgeons such as urologists—we are generally not authorized users. So we need to pair with colleagues either in nuclear medicine or in radiation oncology, and which specialty is kind of location-dependent.

I would say we always pair with radiation oncology to some extent with solid tumors. They're not always involved. And when we think about it, most of us are also pairing with radiology and/or nuclear medicine, at least on the diagnostic side. But these are the types of physicians who have the license to be able to administer these radioactive agents. So that is something that is different. We need to work as a multidisciplinary team.

And another aspect to be mindful of is that we need to take care of the whole patient. So sometimes it's appropriate to turn over the care of the patient to one of these authorized users, a radiation oncologist or a nuclear medicine physician, because some of them know how to take care of the entire patient. Sometimes there's concurrent therapy that can be administered. Sometimes there's supportive care that needs to be administered. So, you know, when we have the setting where they have the expertise to do that, then I think that's fine.

But most of the time, we need to also see the patients because they may be getting additional drugs—you know, underlying octreotide or somatostatin therapy for neuro-income tumors, or GnRH, LHRH agonists or antagonists for prostate cancer, for instance—as well as supportive care, whether we're looking at blood counts and possible transfusions or treating nausea or other symptoms. 

We need to be mindful that we need to also see these patients. If these patients are coming to see us shortly after the treatment, we also need to be mindful that at least the beta-emitting agents, and to a small extent the alpha, will have some gamma irradiation. That's what we see. So, for instance, we inject technetium-99 MDP for a bone scan. That's what's imaged. And these can also be imaged for spec scans, but they also are a risk for the patient's family, the public, as well as our healthcare team. So we need to be mindful of that. And that's particularly for the first couple of days after the administration, when the radioactivity is the highest.

These, all the small molecules at least, are excreted through the kidney. So, especially for that first day, but for several days, we need to be mindful of their urine because, even though most of the rations are within the patient, in the tumors, there's natural shielding from the soft tissue that is there. Once it comes down into the urine, there's no more shielding. So we need to be mindful of that, particularly that first day and then going into the next couple of days. So those are the things that are different in terms of the care of these patients.

But, you know, whether we're talking about a chemotherapeutic, an immunotherapeutic, or some other targeted therapy, if we don't think about them, then the patient is going to miss out on that. That's true of these targeted radionuclide therapies. We need to know that we can order an imaging agent, a diagnostic, to help characterize the tumors and to assess for the appropriateness of this targeted radionuclide therapy, and then take care of the patient afterwards in terms of supportive care, as well as whatever additional imaging needs to be done.

So we have—actually, we still have—some tumor-agnostic indications for strontium and somerium for patients with painful bone metastasis that are largely used for prostate cancer, but it's any indication, in a later line of therapy when we didn't have other things. And that was also true of the initial alpha approved in radium-223. And then, you know, it was kind of in the post-treated setting for lutetium dotatate and then initially for lutetium PSMA-617. 

But these are now all moving to earlier lines of therapy, including with both the lutetium agents, both for Dota-Tate as well as PSMA-617, at the diagnosis of metastatic disease. So, in a “frontline setting”. So we need to be mindful of these. If we don't at least think about them, we're going to miss out. And many patients can have a bigger benefit when we give them up front.