Radiopharma: Comeback of Nuclear Medicine in Oncology

Nuclear medicine never disappeared: it remained clinically relevant but strategically underdeveloped. For decades, its role was largely confined to diagnostics and a limited set of therapeutic indications. However, its underlying capability of delivering highly targeted radiation to cancer cells in ways that conventional therapies cannot was less visible. Today, radioligand therapy is no longer a niche modality. It has become one of the most strategically important areas in oncology, attracting significant capital, reshaping pipelines, and forcing a re-evaluation of how cancer is treated at the molecular level. The science has been established, and the constraint has shifted to delivery.

Long Road Back

In many ways, nuclear medicine is one of the earliest forms of targeted oncology. Iodine-131 was used to treat thyroid cancer in as early as the 1940s. However, for much of the subsequent period, the field remained underutilized, positioned between utility and neglect.

The limitation was not scientific. Radioligand therapy requires a combination of capabilities that few systems historically developed: reliable isotope production, specialized manufacturing, radiopharmacy infrastructure, and clinical environments equipped to handle radioactive drugs. These requirements made the modality operationally complex and capital intensive, with limited commercial precedent.

This equation has now changed. Regulatory approvals received for Lutathera and Pluvicto in 2018 and 2022, respectively, brought radioligand therapy into mainstream oncology. Pluvicto’s VISION trial demonstrated a 38 percent reduction in mortality risk versus standard of care, establishing clear clinical relevance. This shifted radiopharma from a niche capability into a validated therapeutic platform.

Structural Shift, Not Cyclical

Radiopharma is not a transient trend. It represents a structural shift in oncology.

The mechanism is straightforward. Cancer cells often overexpress specific surface targets. Radioligand therapy exploits this by linking a radionuclide to a targeting molecule that selectively binds to these targets. The result is localized irradiation with reduced systemic toxicity. Radiation is delivered from within the tumor environment, rather than externally.

At present, the distinguishing factor is the convergence of three factors: improved targeting molecules, advances in radionuclide selection, and increased willingness from pharmaceutical companies to invest in the required infrastructure. While the concept is not new, its execution is now viable at scale.

From Beta to Alpha: A Step Change in Precision

Most currently approved therapies rely on beta-emitting isotopes such as Lutetium-177. These isotopes are effective but have inherent limitations. Their radiation travels several millimeters, affecting target and surrounding cells.

Alpha-emitting isotopes represent a different profile. They travel only a few cell diameters and deliver significantly higher energy density, leading to irreversible DNA damage within targeted cells. Actinium-225, the most advanced alpha emitter in development, is central to this shift.

Early clinical data from Actinium-225-based therapies, particularly in prostate cancer, suggest meaningful activity even in heavily pretreated populations. The implication is increased potency and improved precision when paired with appropriate targeting molecules.

In parallel, combination approaches are emerging. Radioligand therapy is being explored alongside immunotherapies and other systemic treatments, as part of a broader treatment sequence rather than a standalone modality. This expands its role from a late-line intervention to a potential platform within multi-step oncology strategies.

Strategic Repositioning of Radiopharma

The pharmaceutical industry’s response has been rapid and decisive. Recent acquisitions across major players reflect a clear consensus: radioligand therapy is becoming a core oncology modality.

Novartis established an early lead through its acquisitions of Advanced Accelerator Applications and Endocyte, building an integrated model across manufacturing, development, and commercialization. This approach reflects a key insight: radiopharma requires a distinct operating model rather than an extension of traditional pharmaceutical infrastructure.

Eli Lilly entered the radiopharma arena in October 2023 with a funding of USD 1.4 billion to acquire Point Biopharma. Bristol Myers Squibb made a major radiopharma play in December 2023 with the acquisition of RayzeBio and its Actinium-225-based platform for USD 4.1 billion. Strategic moves such as these acquisitions reinforce the future direction beyond pipeline expansion and signal competition for control over enabling capabilities, particularly isotope supply and manufacturing capacity.

Tthe underlying constraint becomes apparent here. Actinium-225 production remains limited to a few  facilities globally. The challenge is not demand generation but supply scalability, and this imbalance will likely shape competitive dynamics in the near term.

Access Constraint: A Delivery Problem

Unlike most pharmaceutical categories, the primary access barrier in radiopharma is not solely demand or pricing but delivery.

Radioligand therapies are time sensitive. Their half-lives require precise coordination across manufacturing, logistics, and clinical administration. However, many hospitals are not equipped with essentials such as radiopharmacy capabilities, radiation handling infrastructure, and trained personnel.

This creates a geographically concentrated access model. Treatment availability is determined by proximity to qualified centers rather than solely payer coverage. In the United States, Pluvicto’s rollout is constrained by site readiness as opposed to demand.

Reimbursement adds another layer of complexity. Radioligand therapies are priced at roughly USD 40,000 to USD 100,000 per treatment cycle, and a standard course may involve multiple cycles. In most markets, they are covered only for specific label indications, and the pathway to off- label use or earlier line deployment remains tightly controlled by payer criteria. As the field expands into new indications such as gastric, lung, and breast cancer, reimbursement frameworks will need to evolve faster than before.

This represents a shift from a demand-limited model to a supply-constrained one.

Infrastructure Gap: The Defining Constraint

At this point, the scientific case for radioligand therapy is well established, with a rich pipeline and flowing capital. The limiting factor is infrastructure, including the treatment center’s qualification, isotope production upgrade, radio pharma’s capacity, and training of nuclear medicine physicians and radiopharmacists at the volumes required to meet rising demand. These operational challenges will determine the field’s progress.

The strategic implication is clear: infrastructure is not a support function but a competitive asset. The Novartis model, vertically integrated and tightly controlled across manufacturing and supply, may prove to be the template. Companies that heavily rely on external networks for critical components of the value chain may face greater execution risk.

Policy intervention will also play a key role. The US Department of Energy’s investments in expanding the Actinium-225 production capacity at Oak Ridge, along with similar initiatives in Europe, are necessary but likely insufficient relative to the pace of pipeline expansion. While current investments in isotope production are essential, they may not keep pace with clinical development. Misalignment between pipeline growth and supply capacity, may lead to constrained expansion.

Expanding Target Landscape

Current approvals in neuroendocrine tumors and prostate cancer represent only a subset of potential applications. Ongoing research is expanding into a wide range of targets across solid tumors.

Targets such as fibroblast activation protein, HER2, CEA, and B7-H3 are under active investigation. The logic is consistent in each case: identify a surface target overexpressed in cancer relative to normal tissue, design a high-affinity targeting molecule, attach the appropriate radionuclide, and deliver lethal radiation with molecular specificity. The platform is genuinely modular in a way that few oncology modalities are. Once the manufacturing and clinical infrastructure is established, expanding into new targets is, in principle, faster and less expensive than creating an entirely new drug class.

Ultimately, this modularity makes radiopharma one of the most strategically important spaces in oncology over the next decade. It is not just a drug. It is a platform, that could, in principle, be directed at almost any accessible tumor target.

Second Chapter of Radiopharma 

Radioligand therapy has demonstrated clinical efficacy through multiple late-stage trials. The next phase is about execution rather than validation. The current challenge is to scale delivery by expanding isotope supply, increasing treatment capacity, training the workforce, and integrating these therapies earlier into treatment pathways. The key question is no longer whether radiopharma works but whether healthcare systems can build the infrastructure required to deliver it at scale.