In 2018 and 2022, Novartis achieved regulatory approval for two landmark radionuclide drug conjugates (RDCs), Lutathera and Pluvicto, marking the entry of radiopharmaceuticals into a phase of accelerated development.

During the first three quarters of 2025, these two products generated combined sales of approximately USD 2.002 billion, once again drawing strong global attention to the RDC field.

By integrating highly specific targeting ligands with radioactive isotopes, RDCs offer distinct advantages in both diagnosis and therapy and are widely regarded as one of the most promising directions in targeted radiopharmaceutical development.

What Are Radionuclide Drug Conjugates (RDCs)?

Radionuclide Drug Conjugates (RDCs) are a class of therapeutics created by conjugating a targeting ligand—such as an antibody, peptide, or small molecule—with a radioactive isotope via a linker and a chelator.

The core design principle of RDCs is to achieve precise targeting through the ligand, while the radioactive isotope delivers cytotoxic radiation or enables diagnostic imaging.

Owing to this mechanism of action, RDCs offer several advantages in oncology:

• ● High targeting precision with reduced off-target damage: radiation is concentrated at the disease site

• ● Theranostic capability: the same targeting platform can be paired with different isotopes for imaging or therapy

• ● Lower risk of drug resistance: direct radiation-induced DNA damage bypasses conventional resistance pathways

• ● Non-invasive whole-body imaging: enables detection of small or otherwise difficult-to-identify metastatic lesions

Together, these attributes position RDCs as a key growth area in nuclear medicine and precision oncology.

Mechanism of Action and Technical Characteristics of RDCs

First, the targeting ligand—whether an antibody, peptide, or small molecule—binds selectively to specific targets that are highly expressed on the surface of tumor cells. This enables precise delivery of the radioactive isotope to the disease site. These targets are generally expressed at low levels in normal tissues, forming the basis for targeted therapy.

Once the radioactive isotope reaches the target site, it emits α, β, or γ radiation, causing irreversible DNA damage in tumor cells and thereby inducing cell death or inhibiting tumor growth. Different radionuclides exhibit distinct radiation ranges and energy profiles. For example, lutetium-177 (177Lu), a β-emitting isotope, has a moderate tissue penetration range and is well suited for the treatment of solid tumors and metastatic lesions.

From a manufacturing perspective, RDC production is technically complex, involving multiple steps such as ligand synthesis, linker and chelator conjugation, radionuclide production, and radiolabeling. This complexity translates into high technical barriers and underscores the specialized expertise required for RDC development.

Global RDC Pipelines Continue to Expand

In recent years, research and development in RDCs has accelerated, with pipelines increasingly characterized by multiple targets, multiple radionuclides, and a broad range of indications.

To date, 11 RDC products have been approved globally, including nine diagnostic radiopharmaceuticals and two therapeutic agents. Among the most actively pursued targets are PSMA (prostate-specific membrane antigen) and SSTR (somatostatin receptors), which primarily address prostate cancer and neuroendocrine tumors, respectively.

Novartis: A Clear Leader in Radiopharmaceuticals

Novartis is widely regarded as the leading player in the RDC space. Since 2017, the company has rapidly established a fully integrated radiopharmaceutical R&D and commercialization platform through the acquisitions of France-based Advanced Accelerator Applications (AAA) and U.S.-based Endocyte. Radioligand therapies are now positioned as one of Novartis’ four core technology platforms.

In May 2024, Novartis further strengthened its radiopharmaceutical strategy with the acquisition of Mariana Oncology, involving an upfront payment of USD 1 billion and up to USD 750 million in milestone-based payments.

Lutathera (lutetium Lu 177 dotatate)

Lutathera is a lutetium-177 (177Lu)–based radioligand therapy approved by the U.S. FDA in 2018 for the treatment of SSTR–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

The product has since been approved in multiple regions, including the United States, the European Union, France, Canada, and Taiwan. Novartis is also advancing a Phase II study of Lutathera in pheochromocytoma and paraganglioma to expand its clinical indications.

Since launch, Lutathera has demonstrated strong commercial performance, generating approximately USD 724 million in sales in 2024.

Pluvicto  (lutetium Lu 177 vipivotide tetraxetan)

Pluvicto received FDA approval in March 2022 for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The drug employs a small-molecule ligand to target PSMA and delivers a 177Lu radioactive payload for precise tumor irradiation.

In 2024, Pluvicto achieved USD 1.392 billion in annual sales, becoming the first radiopharmaceutical to surpass USD 1 billion in revenue. At the 2025 J.P. Morgan Healthcare Conference, Novartis projected peak sales of more than USD 5 billion for the product.

Clinical-Stage Pipeline

AAA817 (225Ac-PSMA-617)

AAA817 is considered a next-generation follow-on to Pluvicto, utilizing the alpha-emitting radionuclide actinium-225 and targeting PSMA. Compared with beta emitters, alpha emitters deliver higher energy over a shorter tissue range, resulting in more potent localized DNA damage.

The program has initiated two pivotal clinical studies focused on patients with mCRPC.

MC-339

MC-339 is a novel radioligand therapy designed for the treatment of small cell lung cancer (SCLC). The candidate consists of an optimized peptide-based small molecule capable of carrying an actinium (Ac) radioactive payload.

This program reflects Novartis’ efforts to expand beyond PSMA and prostate cancer, broadening the application of its radiopharmaceutical platform across additional tumor types.

Eli Lilly, Bayer, BMS, and AstraZeneca Accelerate Their Entry into Radiopharmaceuticals

Eli Lilly

Through the acquisition of Point Biopharma and strategic collaborations with companies such as Aktis Oncology and Advancell, Eli Lilly has rapidly established a radiopharmaceutical pipeline spanning both PSMA and SSTR targets. Key programs, including PNT2002 and PNT2003, have advanced into Phase III clinical development.

Bayer

Bayer entered the alpha-emitting radiopharmaceutical space early with the launch of Xofigo in 2013 and has since continued to strengthen its focus on targeted alpha therapies (TAT). Several 225Ac-based radiopharmaceutical candidates targeting PSMA and GPC3, including 225Ac-macropa-pelgifatamab (BAY 3546828) and 225Ac-PSMA-Trillium (BAY 3563254),  are currently in clinical development.

Bristol Myers Squibb (BMS)

In 2023, BMS acquired RayzeBio for USD 4.1 billion, gaining access to a radiotherapy platform centered on actinium-225 (225Ac). Lead assets RYZ-101 and RYZ-801 are being developed for neuroendocrine tumors and hepatocellular carcinoma, respectively.

AstraZeneca

AstraZeneca entered the radiopharmaceutical field in 2024 through the USD 2.4 billion acquisition of Fusion Pharmaceuticals. Clinical development is underway for multiple programs, including FPI-2265 (225Ac-PSMA-I&T)  and AZD2068 ([225Ac]-FPI-2068), further expanding the company’s oncology pipeline.

Increasing Demand for High-Quality Excipients in the RDC Era

As RDC development accelerates, the importance of linkers, chelation systems, and molecular modification strategies has become increasingly evident. Extensive studies have shown that polyethylene glycol (PEG) modification can significantly improve the in vivo stability, pharmacokinetics, and safety of peptide-based radiopharmaceuticals. Several RDC candidates in Phase II and III clinical trials have successfully applied PEGylation strategies.

In this rapidly evolving landscape, the availability of high-quality, well-defined, and reliably supplied excipients has become a critical factor for ensuring smooth R&D progress.

With years of experience in PEG derivatives, we provide functionalized PEG linkers designed for RDC applications, including monodispersed PEGs with defined structures, controlled purity, and customizable terminal functionalities. Supported by our established synthesis and purification capabilities, we deliver reliable solutions to support the development and scale-up of radiopharmaceuticals and related conjugated therapies.