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Catherine Meyer: So I want to start by just showing some photos of the new UCLA theranostics center that opened just over a year ago. So it's celebrating a one-year birthday. I think to the outside observer, it may seem like a very simple infusion setup. But of course, we're dealing with radioactive materials, so it's much more complicated than that. And there's much more to the theranostics center than meets the eye.

So of course, in nuclear medicine, we leverage radiation in many forms. We have diagnostic procedures. And I'm just going to focus more on the therapeutic procedures here. While these particles do have very short penetration radii, there's also a co-emission of gamma emissions. And these are also administered at much higher activities.

So some of the basic radiation safety questions that we need to consider. Of course, the internal radiation—what is the dose to the patient? In this talk, we're mostly going to be talking about external exposure, so the dose to others. This can include dose to health care workers or your family members and members of the public.

And so in order to implement theranostics clinically, this requires us to consider the infrastructure that we need to support radioactive materials as well as radioactive patients. So I think I'll just touch on each one of these major topics here, so radiation shielding, patient release, and waste management.

Just a quick note. There are regulatory bodies that set forth these regulations and safety standards related to working with nuclear materials. So the IAEA largely in Europe. And then of course, here in the US, we have the USNRC. And both of these agencies, they put forth safety standards related to radiation protection of patients in the public, exposure limits, equipment QC standards, waste management, and related authorizations.

And importantly, they also set forth requirements for radioactive materials licensing, which is a crucial component for the theranostics clinic. And then of course, with differing regulatory approvals in different countries and differences in clinical practice, the laws and regulations differ for different jurisdictions.

So starting with radiation shielding, we do have a requirement for operational shielding for day-to-day use in the clinic. This involves shielding for syringes and vials, hot lab shielding and portable shields, and of course, shielding for waste storage. But we also need to consider structural shielding, so this includes lead-lined walls and barriers.

Here I'm showing a blueprint of the UCLA clinic design. And I just want to draw your attention to a couple of important components. So in orange here are the infusion rooms. And they all have a private bathroom. And you can also see that they're minimized adjacent rooms where there might be higher occupancy. And then I'm also highlighting the hot lab here.

So for the purpose of shielding calculations, there's a couple of important questions. So you have to know who will be in what space. Is it patients? Is it our staff? Are they radiation workers? Are they not? And how long are they going to be spending in each of these spaces?

We also need to know what therapies are going to be administered and at what activity level. We also need to have an idea of how many patients or what your volume might be. I think it's important to also future-proof these numbers to ensure that you are building in sufficient shielding.

So just looking now into our blueprint here, we can see that we have some recommendations for shielding. So here are two adjacent infusion rooms. I'm pointing to some lead shielding barrier between those adjacent rooms that protect one patient from the patient in the adjacent room.

And then we also opted for unleaded glass on the outside of these infusion rooms, mostly for the visual aesthetics and for the patient experience. But what that led to was that we had additional shielding that surrounded where the staff would remain in the room, including in the glass and the desk barrier.

I also want to draw your attention to this publication that was just released earlier this week that provides some recommendations for shielding specifically for lutetium therapies. And they do provide transmission data for lutetium across various building materials. And they did conclude that it's very likely that you would need shielding.

So in the next topic of patient release, really importantly, there is no standardization among countries for patient discharge. The decision to hospitalize or discharge a patient is based on the maximum likely dose to a member of the public or to a caretaker. And so that dose limit to the public is 1 millisievert per year, and the dose to a caregiver could be up to 5 millisieverts per episode or administration.

What I want to draw your attention to in this table is not one single thing in particular, but just that different organizations put forth different regulatory limits. And these are coming from iodine-131. But this has been the basis for the establishment of regulations for lutetium-177 as well.

And so in terms of inpatient or outpatient therapy, in the US and Australia and many other jurisdictions, lutetium PSMA is primarily an outpatient procedure. However, in Germany, it is an inpatient procedure that requires a minimum of a two-day admission to the nuclear medicine therapy ward. And in radiation protection, this is done for radiation protection reasons and wastewater treatment.

And so the majority of the activity in the circulation, we know it's excreted renally in the first 48 hours, and that is the rationale for the 48-hour admission. There is a chance that there would be a prolonged inpatient stay that may be required. This depends on the consideration of accumulated activity over multiple cycles. And the IAEA does recommend that the duration of any hospitalization should be determined based on an individual patient basis.

Here is a survey conducted among 20 European countries that showed that in these 11 countries that responded about the lutetium PSMA therapy, seven of them do require hospitalization. And in general, across all of these therapies, 65% of the countries do have a regulatory requirement for hospitalization. Here's just another survey that was conducted globally, so not just in Europe. And what they found was that lutetium PSMA was conducted as an outpatient procedure in roughly half of those centers.

Lastly, for waste management, this is a crucial aspect of radiation safety for radiopharmaceuticals. It's a requirement to minimize exposure to the health care workers, to your patients, as well as to the environment. So this includes spent syringes, infusion supplies, and any contaminated materials.

Most commonly, these are all decayed in storage as basically as soon as the radioactivity has decayed, such that it's indistinguishable from the background, that it can be disposed of normally. So typically, after around 10 physical half-lives, around 0.1% of the original activity remains. And this highlights the importance to separate your waste based on physical half-life.

One thing to be aware of is any long-lived radioactive contaminants. So for example, carrier-added lutetium-177 contains a metastable lutetium with a very long half-life of 161 days. And so if that's detectable, you may have to dispose of it as low-level radioactive waste.

Lastly, I want to discuss the ecological considerations. So as part of the German policy for hospital admission, the bodily waste is collected and sequestered for wastewater treatment. In the US, and of course in other outpatient treatment settings, this bodily waste is not controlled, and it's directly disposed of in the sewage. And that relies on a very high degree of dilution of this waste in the wastewater system.

Some countries do elect to collect the urine for some short-term storage. Drawing your attention again to this survey in 20 European countries, they showed that among those 11 centers with lutetium PSMA therapy, only four of them did have some requirement for special wastewater treatment. And so really, only a few countries do have specific criteria set forth for wastewater treatment.

So in summary, we have agencies such as the IAEA and USNRC to regulate nuclear materials. Your theranostics facility must meet infrastructural shielding requirements. Importantly, there's no standardization across countries about the discharge of patients and whether it is an inpatient or outpatient procedure.

With the projected increase in patient volumes, you should consider the capacity of your infrastructure and how your mechanisms for patient and waste management meet those projected increases. And of course, proper handling of waste is in the best interest of our patients, our personnel, and the environment.