The next phase of radioligand therapies is about execution

Radiopharmaceuticals, designed to deliver small doses of radiation to targeted cells while minimizing damage to healthy tissue, have reached an inflection point. Once largely reserved for late-line oncology settings, radioligand therapies (RLTs) are now drawing increasing attention from drug manufacturers, driven by clinical data demonstrating meaningful benefit across a range of cancers.

Key to this momentum are studies of RLTs showing efficacy in earlier lines of treatment with therapeutic effects no longer confined to patients with advanced disease or those who have exhausted conventional treatment options. As pipelines expand, manufacturing reliability is as critical as clinical efficacy.

Still, RLTs remain constrained by an obstacle unique to this advanced modality: time. The radioactive half-lives of therapeutic isotopes impose narrow manufacturing and delivery windows, leaving little margin for error if therapies are to be administered effectively. In addition, manufacturers must manage radionuclide supply, radiolabeling, quality testing, batch release, and logistics — with each step requiring precise execution and careful coordination to ensure a therapy reaches the patient in a timely manner.

As radioligand therapies move into earlier lines of treatment and broader patient populations, the industry’s focus is shifting decisively from scientific validation to operational execution. Success in the next phase will depend not only on the strength of the molecule, but on the ability to manufacture, release, and deliver these therapies reliably — at scale, and without delay.

Key considerations for scalable RLT manufacturing

Critical questions facing the RLT space now center around if they can be manufactured, released, and delivered reliably at scale.

Manufacturers developing RLTs must make foundational decisions early to determine whether a therapy can scale successfully. According to Scott Holbrook, chief commercial and manufacturing officer at Ratio Therapeutics, successfully accomplishing this includes selecting a radionuclide that has characteristics that marry up with a targeting strategy — and can be reliably sourced at scale — as well as considering stability challenges such as radiolysis, in which emitted radiation destabilizes or degrades the drug product. Also important is designing manufacturing processes and determining the appropriate timing for scale-up with commercialization in mind.

Holbrook emphasized that neglecting these considerations until late-stage development can introduce significant regulatory and operational hurdles. Changing a drug product or manufacturing process after a pivotal study, for example, can trigger regulatory comparability requirements, potentially resulting in additional studies and delaying commercialization.

“You want to think prospectively about conducting those activities ahead of the pivotal trial, so you can introduce drug manufacturing — with all the relevant activities — into the pivotal trial, so the data the FDA is reviewing reflects the drug product the company intends to take forward into the post-approval setting,” he says.

From clinical success to operational reality

The constraints surrounding radioligand therapies are also apparent in the repetitive nature of manufacturing these medicines, which is driven by their short beyond-use dating. The objective is not simply to demonstrate efficacy, but to ensure a therapy can be manufactured, released, and delivered reliably and consistently once it reaches the market.

“Depending on the uptake of your product, you not only have to successfully execute the manufacturing of a scaled-up commercial batch on a weekly or almost daily basis, but you also have to replicate all of the manufacturing activities — such as access to raw materials, shipping logistics, and delivery to the end-user hospital or clinic,” says Holbrook.

This reality is reshaping how developers approach RLT design and development. Increasingly, decisions around radionuclide selection, formulation stability, and process automation are being made earlier in the lifecycle, with an eye toward commercial execution rather than clinical proof alone.

Across the industry, this shift has prompted greater emphasis on platform-level innovations that address pharmacokinetics, in vivo stability, and manufacturability in parallel. Rather than treating drug design and manufacturing as sequential challenges, developers are integrating these considerations from the outset, recognizing that in radiopharmaceuticals, operational readiness is inseparable from therapeutic success.

One example of this approach can be seen in technologies designed to improve both drug behavior and manufacturability. Ratio Therapeutics’ Trillium platform illustrates how developers are engineering radioligand therapies with downstream execution in mind. Trillium incorporates a tunable structural motif that allows compounds to reversibly bind to albumin, enabling modulation of pharmacokinetics to improve tumor exposure while limiting off-target accumulation to protect critical organs.

Importantly, these types of platforms reflect a broader industry trend rather than a single-company solution: designing radiopharmaceuticals that balance biological performance with manufacturing feasibility from the earliest stages of development.

Logistics reshape where radiopharmaceuticals are built

The importance of transportation logistics — driven by the short half-lives of therapeutic isotopes — has begun to shape the physical footprint of the radiopharmaceutical industry itself. Developers and manufacturers are increasingly clustering production around locations that minimize transit time and reduce supply-chain risk.

According to Holbrook, three primary hubs have emerged: Indianapolis, Indiana; Salt Lake City, Utah; and the broader New York-New Jersey metropolitan area. Indianapolis emerged as an early hub due to its robust air transportation infrastructure and proactive state-level efforts to attract radiopharma investment.

Earlier this year, Indiana was bestowed the title of Radiopharmaceutical Capital of the World; BioCrossroads, a life sciences initiative based in Indianapolis, led the effort to trademark the designation through the USPTO.

Meanwhile, the Salt Lake City region has gained momentum as an emerging hub, supported by favorable air logistics and proximity to Nusano, a manufacturer of radionuclides. Co-locating manufacturing near isotope production helps reduce the risk associated with the earliest and most time-sensitive stages of transport.

In May 2025, Ratio Therapeutics signed an agreement with the Wasatch Group to construct a 65,000-square-foot radiopharmaceutical research and manufacturing facility in Salt Lake City. The facility will be part of the Wasatch Group’s Medical Innovation Technology Research Campus and is expected to be fully operational by late 2027. The new site will enable Ratio to vertically integrate its pipeline of radiopharmaceuticals for cancer treatment and monitoring, with capabilities for end-to-end production and commercial-scale manufacturing.

“These hubs are helpful for the industry as a whole,” Holbrook notes. “They help build a workforce of experts who can manufacture the product, strengthen the supply chain, and reduce fragmentation — particularly in regions accustomed to handling these specialty drugs on a frequent basis.”

Last month, Michigan-based Niowave expanded its existing supply agreement with AstraZeneca to a 10-year commitment to provide medical isotope Actinium-225 (Ac-225) to advance AstraZeneca’s growing portfolio of radioconjugates. While Ac-225 is one of the most promising radioisotopes in oncology, the global supply is limited. Niowave’s proprietary superconducting linear accelerator technology and radiochemistry provide sustainable, U.S. production to address this need, according to the company.

Workforce: The next constraint on scale

As radioligand therapies move toward broader commercialization, workforce readiness is emerging as another critical factor shaping the modality’s growth.

While radiopharmaceutical manufacturing shares many similarities with traditional pharmaceutical operations, it also requires specialized expertise unique to this field. Holbrook highlighted the importance of roles such as radiation safety officers, radiochemists, and radiopharmacists, which sit alongside more familiar functions including manufacturing technicians, quality professionals, and validation engineers.

“We’re hoping to continue increasing talent proportionate to the need in the RLT space,” Holbrook adds. “We’re still okay from a capacity and manpower standpoint today, but we’re expecting a large wave of drug products in the coming years.”

Mirroring expansion across other advanced modalities amid broader onshoring initiatives, workforce development is becoming a forward-looking exercise for drug manufacturers. Companies are increasingly focused on building talent pipelines ahead of anticipated growth curves, recognizing that in radiopharmaceuticals, scaling too late — whether in facilities, supply chains, or people — can quickly become a bottleneck to patient access.

Contract development and manufacturing organizations (CDMOs) with capabilities in handling radiopharmaceuticals are seeing strong demand, reflecting strength in these therapeutic modalities, according to CPHI’s 2024 annual report. “Barriers to entry here are extremely high and could lead to a supply/demand imbalance in the near term as more radiopharmaceuticals make their way into the clinical pipelines,” according to CPHI.

In January 2025, Lantheus Holdings announced plans to buy radiopharma CDMO and diagnostics company Evergreen Theragnostics in an all-cash deal valued at $250 million. The acquisition has bolstered Lantheus’ capabilities as a fully integrated radiopharmaceutical company, incorporating Evergreen’s scalable RLT manufacturing infrastructure which includes a revenue-generating CDMO business.

In April, radiopharma CDMO PharmaLogic Holdings announced it was acquiring a majority stake in Agilera Pharma AS from the Institute for Energy Technology (IFE) in Norway. At the time, PharmaLogic said Agilera was one of only two CDMOs worldwide currently manufacturing radiopharmaceutical therapeutics.