Imagine treating cancer with something as precise as a guided missile—radioactive payloads delivered only where they're needed most. Radiopharmaceuticals are redefining both diagnostics and therapeutics, creating new momentum in oncology by pairing tumor-seeking molecules with potent radioisotopes. But what does it really take to develop these agents, and why are investors and scientists alike turning their attention to this field?

In this episode of Smart Biotech Scientist Podcast, David Brühlmann  sits down with Bryan Miller, Director of Scientific and Technical Operations at Crown Bioscience UK, a Contract Research Organization (CRO) specializing in translational oncology and immuno-oncology drug discovery and development.

Key Topics Discussed

• Oncology discovery research is unpredictable, with shifting views on what targets are druggable.
• Bryan Miller transitioned from cardiac research to oncology to help develop new cancer therapies.
• Crown Bioscience supports oncology drug development through diverse, advanced preclinical models.
• Radiopharmaceuticals combine targeting, imaging, and therapy in a single approach.
• Theranostics enable safer, more precise treatment and faster patient stratification.
• The radiopharmaceutical field is rapidly expanding due to scientific and commercial momentum.
• Data-driven model selection is critical to reducing risk in preclinical development.
• Radiopharmaceutical development brings unique challenges requiring specialized expertise and partnerships.

Episode Highlights

• Bryan Miller's path from cardiac disease research to leading preclinical cancer model development [03:03]
• The broad range of cancer models available at Crown Bioscience, from organoids to PDX and humanized in vivo models [04:05]
• How radiopharmaceuticals differ from traditional chemotherapies in terms of safety and speed, including the concept of theranostics [07:32]
• The reasons behind the surge of interest in radiopharmaceuticals within science and industry [09:04]
• The importance of selecting the right preclinical model for success—and how AI and big data are starting to play a role [10:11]
• Critical pitfalls and unique technical challenges in radiopharmaceutical drug development [11:17]
• Crown Bioscience’s collaborative approach with Medicine Discovery Catapult to navigate the complexities of radiopharmaceutical research [13:35]
• The diverse client needs, from small startups to global pharma companies, and how mature their development programs can be [14:20]
• Strategies for scaling preclinical and translational capabilities to meet growing demand in radiopharmaceutical studies [16:04]

In Their Words

Radiopharmaceuticals are diagnostic and therapeutic agents. So they consist of a targeting agent—typically a small molecule or an antibody—and this will target the tumor. There’s also a radionuclide, and there’s a linker that connects the two. The radionuclide can act as either an imaging agent for diagnosis of cancer or as a therapeutic agent, where the radionuclide delivers a lethal dose of radiation to the tumor.

Episode Transcript: Mastering Radiopharmaceutical Development: Preclinical Model Selection for Clinical Success - Part 1

David Brühlmann [00:00:27]:
What if the next breakthrough in cancer treatment isn’t a pill or an infusion, but a precisely targeted radioactive payload that hunts down tumor cells like a guided missile? Today we’re diving into the radiopharmaceutical revolution with Bryan Miller, who is the Director of Scientific and Technical Operations at Crown Bioscience UK. From his early days studying colorectal cancer models to now leading preclinical development for one of oncology’s hottest therapeutic classes, Bryan is taking us inside science that’stransforming how we fight cancer.

Welcome, Bryan, to the Smart Biotech Scientist Podcast. It’s good to have you on today.

Bryan Miller [00:02:25]:
It’s great to be here, David.

David Brühlmann [00:02:27]:
Bryan, share something that you believe about early discovery research that most people disagree with.

Bryan Miller [00:02:34]:
So I’ve found that research progress is rarely linear or predictable. Over my career, I’ve seen the undruggable become druggable. I’ve seen false starts in some areas and surprisingly rapid advances in others. And I think that’s why I find it so dynamic and exciting—and why I love being a part of it.

David Brühlmann [00:02:51]:
Excellent. Draw us into your story. Tell us what sparked your interest in working on cancer models, and then what were some interesting pit stops along the way that got you to your current role?

Bryan Miller [00:03:03]:
Yeah, it’s quite interesting. So my PhD was actually in cardiac disease. So that’s where I started out. It was when I did postdoctoral fellowships—first at the University of Toronto and the second at the Beatson Institute (UK)—that really took me towards oncology models, both in vitro and in vivo. My postdocs were focused on models of colorectal and pancreatic cancer. And I think what motivated me at that point is exactly the same as what motivates me now. I was passionate about contributing to the development of new therapies for cancer and identifying new therapeutic targets. And really that’s what motivates me to go to work every day to this day. Being part of Crown Bioscience allows me to work across a large array of different cancer indications with a diverse range of clients. And it’s really motivating when you’re contributing to the development of new therapies. It’s fantastic when you’ve contributed to a research program that has led to a therapy going into the clinic.

David Brühlmann [00:03:58]:
Tell us a bit more about your current work. What does that look like when you’re developing these new therapies?

Bryan Miller [00:04:05]:
So we are a preclinical contract research organization, oncology focused, but we do work with a large array of different clients working on various therapeutic types. We have a range of advanced preclinical models available to our clients to run their research programs with. We work across most cancer indications and across most therapeutic types. So it’s a very diverse area of work that we conduct at Crown, which makes it really interesting. It’s very varied, it’s very interesting, and it’s absolutely fantastic to support this variety of client research projects.

David Brühlmann [00:04:42]:
And when you say it’s very diverse, that includes the various diseases you’re working on, and I imagine also very diverse companies with very diverse needs. Before we dive a bit further into radiopharmaceuticals, what is the main need companies have when they come to you? What is the main problem they want to solve?

Bryan Miller [00:05:04]:
They typically come to us with a target in mind and usually with a therapeutic that they wish to test. One of our main roles is to guide them towards the most appropriate preclinical model to address the question they’re asking. We have a range of different models available. We’ve got an excellent array of in vitro models, and we’re particularly well known for our organoid platform. So certainly at the in vitro phase, we have advanced models that can be very valuable. We’re also very well known for our PDX library. We have PDX models that cover most cancer indications, and we have genomic data associated with them. If you have targets in mind, we can guide you towards the most appropriate PDX model for your work. In addition, we have an array of TDX models, genetically engineered models, and humanized models. So really, while we’re cancer focused, for most questions around the development of cancer treatments—including neuro-oncology therapies—we will have appropriate models to support your research program and help you filter down to the most relevant ones.

David Brühlmann [00:06:08]:
When you say models, are these animal models, or are these 2D cultures, 3D cultures, or a combination of various models?

Bryan Miller [00:06:16]:
All of that, actually. So yes—2D cell culture, 3D cell lines, organoids, and various in vivo models. That includes syngeneic models, CDX models, PDX models, and humanized models. So it really is quite a wide array.

David Brühlmann [00:06:31]:
Excellent. So let’s dive into one specific area—radiopharmaceuticals. A lot of our listeners, I imagine, are not familiar with that. Can you start with the basics? What are radiopharmaceuticals, and how do they differ from traditional cancer therapies?

Bryan Miller [00:06:52]:Yeah, so radiopharmaceuticals are diagnostic and therapeutic agents. They consist of a targeting agent—typically a small molecule or an antibody—which targets the tumor. There’s also a radionuclide, and there’s a linker that connects the two. The radionuclide can act as either an imaging agent for the diagnosis of cancer or as a therapeutic agent, where the radionuclide delivers a lethal dose of radiation to the tumor.

David Brühlmann [00:07:18]:
Can you elaborate a bit more? Give us an example. How are they different from a traditional cancer therapy? Is it the morphology, the mechanism, or what exactly are the main differences?

Bryan Miller [00:07:32]:
I’d say there are probably two real advantages of radiopharmaceuticals. The first is safety, because you’re dealing with a therapeutic that can very specifically target a tumor. One of the early stages is to characterize the level of accumulation within the tumor and make sure you don’t have accumulation in other organs of the body. So they can have a greater safety profile than more traditional therapies. That’s one advantage.

The other thing that distinguishes them is the idea of theranostics. You can use an agent that combines diagnostics with therapy, using the same scaffold. You can use one radionuclide to diagnose a tumor and then switch to a second radionuclide to target and kill the tumor. Because you’re combining those within the same strategy, this allows for really good stratification of patients and very rapid progression from diagnosis through to therapy.

David Brühlmann [00:08:28]:
Okay, I see. So it’s faster, and there are a lot more things happening in parallel, giving you a much broader picture.

Bryan Miller [00:08:36]:
Yeah, and I think safer as well. A lot of them are much safer than traditional chemotherapies.

David Brühlmann [00:08:41]:
The radiopharmaceutical field has gone from a niche therapy to one of the hottest areas in oncology. What’s driving this rapid transformation, both on the scientific side and on the commercial and investor side?

Bryan Miller [00:09:04]:
That’s what we’re finding as well. There does seem to be growing interest in the area. It’s quite dynamic right now, and there are a lot of exciting things happening. I think it goes back to some of the advantages I just described, particularly the theranostic approach, which gives these therapies a considerable advantage.

I think the safety profile is another aspect that a lot of companies we work with find very valuable during development. And maybe the third aspect is the widening range of cancer indications that radiopharmaceuticals are being applied to. We’re starting to see more radiopharmaceuticals coming through that target a much more diverse range of cancers.

David Brühlmann [00:09:44]:
And the main purpose of all that is basically to make faster, more actionable, and more predictive decisions with all your models. I’m curious—on top of your models, do you add a layer of machine learning, AI, or advanced data-driven approaches? How does that work in your field.

Bryan Miller [00:10:05]:

In terms of model selection?

David Brühlmann [00:10:08]:
Yeah, and also in terms of interpretation of the data.

Bryan Miller [00:10:11]:
I would say that is certainly applicable to the selection of models. It’s absolutely crucial—you need to get your preclinical model right in order to have a successful research program. We have large datasets associated with all of our models. So certainly, if you’re looking for particular targets or particular gene profiles, we can help you with that. Our models are very well characterized, and that’s information we’re happy to share to guide you towards the most appropriate model.

We’re also very excited by the prospect of AI. I think that’s something that’s much more common now, and it’s something we’ll be incorporating into workflows as well.

David Brühlmann [00:10:51]:
Yeah, you’re making a very good point—you have to select the right preclinical model, because that’s the foundation, isn’t it?

Bryan Miller [00:10:59]:
Exactly. Yes. If you get the order wrong, you’re not going to have a successful program.

David Brühlmann [00:11:02]:
Yes. You’re going to answer the wrong question at the end of the day if you choose the wrong model. Besides that, what are other pitfalls when developing a new drug? What other choices or strategies really have to be right?

Bryan Miller [00:11:17]:
Yeah, particularly in the radiopharmaceutical field, it can be quite a challenging area. One early point is getting the targeting strategy for the tumor correct. That’s a very important aspect—you need high specificity in tumor targeting.

You also need to select an appropriate isotope and the correct labeling position and labeling strategy. Another important aspect is ensuring that you either have, or are working with someone who has, a reliable source of radionuclides. These materials have to be labeled fresh before dosing, so the supply needs to be reliable.

It’s also really crucial to have a robust labeling strategy and to ensure that proper and thorough quality control (QC) is performed on the labeled material. Nothing should be dosed unless it passes stringent QC tests. And, as we discussed, making sure that the model you select is the most appropriate one is critical to giving you the best chance of success.

These are all areas where we can assist—providing advice, guidance, and helping to design the most appropriate study design.

David Brühlmann [00:12:24]:
And compared to conventional drug development, what are the unique challenges associated with radiopharmaceutical development? You’ve mentioned quite a few things that need to be right. How different is radiopharmaceutical development compared to conventional drug development, and what are the unique challenges?

Bryan Miller [00:12:46]:I mean, obviously there are some commonalities. But I think the unique challenges are the need to prepare material fresh—you can’t make it in bulk and store it. You have to have fresh material that can be dosed almost immediately. There’s also the complexity of some of the strategies, particularly designing an appropriate radiolabeling strategy. Because this is quite a specialized area, you really need to work with people who have specialist expertise and can advise on the most appropriate way to label the molecule, the correct isotope to use, and, crucially, the linker. Those are all aspects of radiopharmaceutical design that are absolutely critical for success.

David Brühlmann [00:13:26]:
And how do you, as a company, manage all that and navigate these difficulties? What are some specific approaches you’ve developed?

Bryan Miller [00:13:35]:
One absolutely crucial element is the collaboration we’ve established with Medicines Discovery Catapult (MDC). We’ve recently launched this strategic collaboration, which brings together the range of preclinical models and preclinical expertise from Crown Bioscience with the radiolabeling expertise and radiopharmaceutical experience from MDC. It’s a really strong partnership, combining complementary strengths to deliver highly successful radiopharmaceutical studies for our clients.

David Brühlmann [00:14:10]:
And what kind of clients do you usually work with? Are they small companies, mid-sized companies, or large pharma organizations?

Bryan Miller [00:14:20]:
All three, actually. We work with a diverse range of clients—small, medium, and large. As we’ve alluded to earlier, there’s growing interest in the radiopharmaceutical field, so we’re seeing more and more organizations approaching us to discuss radiopharmaceutical development and appropriate strategies for further studies. That ranges from quite small companies through to larger pharma organizations.

David Brühlmann [00:14:39]:
I imagine their needs are quite diverse. Can you give us a sense of how those needs differ between small biotech and large pharma? What are the typical differences?

Bryan Miller [00:14:53]:
One of the main differences we see is the maturity of the program. Some clients approach us at a very early stage, without a defined radiolabeling strategy. In those cases, we may need to do significant optimization work—guiding isotope selection, developing the labeling strategy, and performing validation to ensure the material can be labeled effectively and is suitable for use.

Other clients come to us with more mature programs. They may already have an optimized labeling strategy and a defined protocol. In those cases, our role may be to perform the labeling through protocol transfer, rather than developing the process from scratch. So those represent two quite different types of client needs that we commonly see.

David Brühlmann [00:15:42]:
Since interest in radiopharmaceutical development is increasing on both the scientific and business sides, I imagine demand is growing rapidly. How do you ensure that you can scale your preclinical and translational capabilities to meet that demand?

Bryan Miller [00:16:04]:
We have a lot of experience in this area. Both Crown Bioscience and Medicines Discovery Catapult have worked in our respective fields for many years, and we’re accustomed to running a wide array of projects simultaneously. Scalability is something we’re very experienced with.

You’re absolutely right—we’re seeing increasing demand for these types of studies. But we approach scalability in the same way we do for other programs: scaling our in vivo and preclinical capabilities on the Crown side, and scaling the radiolabeling and radiochemistry capabilities on the MDC side. Both partners bring significant experience in delivering complex studies at scale.

David Brühlmann [00:16:43]:
That’s where we’ll pause for today. In Part Two, we’ll explore the specific platforms accelerating radiopharmaceutical translation and get Bryan’s predictions on where this field is heading. If you’re finding value in these conversations, please leave us a review on Apple Podcasts or your favorite platform.

It helps other biotech scientists like you discover the show. See you in Part Two.

Alright, smart scientists—that’s all for today on the Smart Biotech Scientist Podcast. Thank you for tuning in and joining us on your journey to bioprocess mastery. If you enjoyed this episode, please leave a review on Apple Podcasts or your favorite podcast platform. By doing so, we can empower more scientists like you.

For additional bioprocessing tips, visit www.bruehlmann-consulting.com. Stay tuned for more inspiring biotech insights in our next episode. Until then, let’s continue to smarten up biotech.

Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.

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About Bryan Miller

Bryan Miller is Director of Scientific and Technical Operations at Crown Bioscience. He completed his PhD in Biochemistry at the University of Leicester, followed by two postdoctoral fellowships at the University of Toronto and the Beatson Institute. During this time, his research focused on the development and application of in vivo and in vitro models of colorectal and pancreatic cancer.

Since 2015, Bryan has worked in the contract research organization (CRO) sector, supporting oncology drug discovery and development programs across a range of therapeutic modalities. He joined Crown Bioscience UK in 2019, where he leads scientific and technical operations, leveraging advanced preclinical models to help clients progress innovative cancer therapies toward the clinic.

Connect with Bryan Miller on LinkedIn.

He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.  

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