Radiopharmaceuticals are entering a new phase in oncology, moving from a long-established nuclear medicine modality into a growing precision cancer therapy field.
These therapies use targeting molecules to deliver radioactive payloads to diseased tissue, allowing clinicians to both visualize and treat tumors through a theranostic approach. While radionuclides such as iodine-131 have been used in medicine for decades, newer targeted radiopharmaceuticals such as Lutathera and Pluvicto have helped bring the modality further into mainstream oncology practice.
More than 60 radiopharmaceuticals have been approved for diagnosis or treatment across cancer, neurodegenerative and cardiovascular diseases, with therapeutic radiopharmaceuticals currently centered largely on oncology.
Chief Commercial and Manufacturing Officer
Ratio Therapeutics
Xtalks spoke with D. Scott Holbrook, Chief Commercial and Manufacturing Officer at Ratio Therapeutics and Chief Strategy Officer and General Manager at PharmaLogic, about the operational realities of scaling radiopharmaceuticals and the manufacturing considerations shaping Ratio Therapeutics’ development strategy. PharmaLogic has partnered with Ratio Therapeutics to support manufacturing and supply chain solutions for its next-generation radiopharmaceutical pipeline.
For companies developing next-generation precision radiopharmaceuticals, manufacturing is not a back-end consideration. It is closely tied to clinical trial execution, commercial scalability, patient access and even drug design.
Ratio Therapeutics is developing next-generation precision radiopharmaceuticals for solid tumors, with a focus on areas of high unmet clinical need. Its lead therapeutic program, [Ac-225]-RTX-2358, is a fibroblast activation protein-alpha (FAP)-targeted radiotherapeutic labeled with actinium-225. The therapy is being evaluated in the ATLAS trial, a Phase I/II open-label study in patients with relapsed or refractory soft tissue sarcomas that express FAP.
Ratio announced in December 2025 that dosing of the first cohort had been completed in the study. The ATLAS trial is designed to assess safety, tolerability, dosimetry, biodistribution, pharmacokinetics and preliminary anti-tumor activity. Patients must first be assessed for FAP expression using a [Cu-64]-LNTH-1363S PET scan, reflecting one of the defining advantages of radiopharmaceutical development: the ability to image the target before delivering therapy.
Holbrook said Ratio’s broader strategy is to design “fit-for-purpose” radioligand therapies and diagnostics with what he described as tunable pharmacokinetics, or the ability to adjust how long a drug remains in circulation.
This is intended to give the drug “multiple opportunities to pass by a target on a tumor and more effectively target the tumor,” he explained.
Ratio’s Trillium platform is designed to enable pharmacokinetic modulation to improve drug availability, tumor delivery and tumor loading. The company has also described its platform as radionuclide agnostic, meaning different radioactive payloads can be evaluated and selected based on the drug candidate, indication and desired therapeutic profile.
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The Core Challenge: Target the Tumor, Spare Healthy Tissue
One of the central challenges in radiopharmaceutical development is improving tumor targeting and tumor retention while minimizing radiation exposure to healthy tissue.
“The goal of doing this is to both improve the efficacy of the drug while at the same time also improving the safety profile,” Holbrook said.
That balance is especially important as companies explore alpha-emitting radionuclides such as actinium-225. Alpha emitters can deliver highly potent radiation over a short path length, which may be advantageous for tumor cell killing but also places pressure on drug design, dosimetry, manufacturing controls and supply chain reliability.
In this context, pharmacokinetics is directly tied to the therapeutic index. If a drug clears too quickly, it may not remain in circulation long enough to reach tumor targets effectively. If it circulates too long or accumulates in non-target tissues, safety risks may increase.
Why Scaling Radiopharmaceuticals Is Different
Radiopharmaceutical manufacturing differs from traditional small molecule or biologic production because time is always working against the product.
“One of our obvious challenges is the shelf life,” Holbrook said. “We need to extend the shelf life of the radiopharmaceutical as much as possible for it to have a useful commercialization and distribution footprint.”
Because radioactive materials decay over time, manufacturers must account not only for drug stability, but also for the half-life of the radionuclide itself. Holbrook explained that companies must scale both the radioactive concentration and the usable shelf life of the drug product.
Another challenge is radiolysis, a process in which the radioactive payload itself can degrade the drug. That means developers must run formulation and stabilization experiments to keep the drug intact at the highest feasible concentration for the longest possible period, while still meeting release specifications.
“The goal is to have a scaled-up drug product that has a long enough shelf life for commercial distribution at normal temperature storage conditions, if possible, by the time we’re in the midst of a Phase III or a pivotal clinical trial,” Holbrook said.
The timing of these activities is strategic. Performing scale-up studies too early can create significant cost pressure, particularly because some radionuclides are expensive and difficult to obtain. But waiting too long can also create risk. If the commercial formulation differs meaningfully from the early clinical formulation, regulators may require additional comparability or bioequivalence work.
Location as a Key Manufacturing Variable
For radiopharmaceutical companies, site selection is not just about real estate. It can influence manufacturing resilience, radionuclide access, regulatory timelines and delivery to clinical sites or hospitals.
Holbrook said several factors are critical when evaluating locations for radiopharmaceutical manufacturing. Proximity to a major airport hub is one of the most important, since radioligand therapies are often shipped by air across North America and globally.
The availability and affordability of space also matter, particularly because some facilities may require large footprints and future expansion capacity.
Proximity to radionuclide starting material is another key variable. The farther a radionuclide must travel before drug manufacturing even begins, the more decay occurs and the greater the logistical risk.
“From the time it’s produced and at its point of origin and shipped to a drug company like Ratio, it begins to decay away and there’s less and less available over time,” Holbrook explained.
Workforce and regulatory infrastructure are also essential. Radiopharmaceutical facilities require people with expertise in aseptic manufacturing, pharma operations, radiochemistry and radioactive materials handling. Skilled contractors are needed to build specialized facilities, while state and local regulatory environments can affect radioactive materials licensing, zoning and permitting timelines.
Manufacturing Partnerships and Last-Mile Logistics
Ratio’s collaboration with PharmaLogic is designed to support both manufacturing redundancy and decentralized distribution. PharmaLogic announced in December 2025 that it had supplied the first cohort dosing for Ratio’s ATLAS trial from its Bronx, New York, radiopharmaceutical manufacturing facility. The company said its broader network includes more than 45 facilities across the US, Puerto Rico, Canada and Norway.
According to Holbrook, this type of network can be important because radiopharmaceuticals require more than manufacturing capacity. They require last-mile logistics that can reliably move short-lived therapies to clinics and hospitals.
The decentralized network model can help reduce single-site dependency and support distribution to institutions already equipped to handle nuclear medicine products. This may become even more important as the field moves toward more personalized approaches, where patient-specific dosing could make radiopharmaceutical therapy look increasingly like a prescription-based pharmacy activity.
Clinical Trial Supply Adds Another Layer of Complexity
Many of the same hospitals that administer commercial radiopharmaceuticals may also participate in clinical trials, but investigational supply introduces added uncertainty.
Clinical trial patients must meet strict inclusion and exclusion criteria, and for radiopharmaceutical studies, they may also need diagnostic imaging to confirm that the relevant target is present. This can create uncertainty until screening is complete.
Holbrook noted that many patients entering radiopharmaceutical trials may have exhausted conventional treatment options and may be very sick by the time they are screened. As a result, patients may need to drop out or be rescheduled unexpectedly.
Early-phase manufacturing can also be less predictable than commercial production because final scaled-up procedures may still be under development. This can lead to higher manufacturing failure risk earlier in development, before processes are fully optimized and validated.
For radiopharmaceuticals, these clinical and manufacturing variables are closely connected. A delayed patient visit, failed batch or shipping disruption can have greater consequences when the product has a short shelf life and is decaying in real time.
The Future of Radiopharmaceutical Networks
Despite these challenges, Holbrook said the radiopharmaceutical field has an important advantage: much of the long-lead infrastructure already exists.
Nuclear medicine is a well-established modality, and many regions already have radiopharmacy networks, trained personnel and regulatory frameworks that can support diagnostic and therapeutic radiopharmaceuticals. Radioiodine therapy for thyroid cancer, for example, has long been handled through established radiopharmacy and logistics systems.
“I don’t think it’ll be a huge lift,” Holbrook said. “There are some nuances. There may be some additional pieces of equipment, for example, that might be needed, but I think a lot of the expertise is in place.”
As radioligand therapy becomes more personalized, radiopharmacy networks may play an even larger role. Patient-specific dosing could require pharmacy-level capabilities, state-specific licensing and facilities equipped to prepare and distribute individualized radiopharmaceutical products.
For the next wave of precision radiopharmaceuticals, success will depend not only on finding the right target or radionuclide, but also on building the manufacturing and distribution networks needed to deliver these therapies consistently.
As companies like Ratio Therapeutics advance FAP-targeted programs and other solid tumor radiopharmaceuticals, the field’s future will be shaped as much by logistics and regional infrastructure as by radiochemistry itself.
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