The radiopharmaceutical revolution: a review of the field

Radiopharmaceuticals are a rapidly evolving class of drugs that combine radioactive isotopes with biological molecules to target and treat specific diseases, most notably in oncology and neurology. These agents have a dual role: as diagnostic tools, they help locate and visualize tumors or diseased tissue while as therapeutic agents, they deliver targeted radiation to destroy those same cells.

Over the past few decades, radiopharmaceuticals have undergone a significant transformation. Initially, these drugs were primarily used for imaging, allowing for early diagnosis of cancers and other diseases.

However, the emergence of theranostics, a combination of therapy and diagnostics, has revolutionized the field. Theranostic agents can both detect and treat diseases, offering a more personalized approach to medicine. As Brian Markison, chief executive officer (CEO) of Lantheus – a leading radiopharmaceutical-focused company – pointed out, “Radiopharmaceuticals can find, fight and follow. These agents have the unique capability to target specific cancer cells, provide diagnostic imaging, and deliver targeted therapeutic radiation to destroy cancer cells.”

The growth of the radiopharmaceutical field has been exponential – a Statista market research report indicates it is expected to reach $14 billion by 2032, while it is valued just below $7 billion today. “This growth will be driven by innovations in both diagnostic and therapeutic radiopharmaceuticals, the increasing number of patients treated, and the expanding application of these technologies in various cancers and in neurology,” added Markison.

So without further ado, let’s delve into the accelerating field of radiopharmaceuticals.

Radiopharmaceutical mechanism: Find, fight, follow

Radiopharmaceuticals are emerging as a powerful class of precision medicine, capable of “finding,” “fighting,” and “following” cancer cells. This concept, as explained by Markison, underpins their mechanism of action. Radiopharmaceuticals consist of a targeting agent that binds to a specific biological target on cancer cells, coupled with a radioactive isotope. This combination allows for precise delivery of radiation to the tumor while minimizing harm to surrounding healthy tissue. This approach enables the drugs to seek out cancer cells, destroy them with targeted radiation, and then track the effectiveness of the treatment.

In the “find” stage, the radiopharmaceutical binds to cancer-specific antigens or receptors, such as prostate-specific membrane antigen (PSMA) in prostate cancer treatments. The attached radioactive isotope emits gamma radiation, detectable by imaging technologies like PET (positron emission tomography) or SPECT (single-photon emission computed tomography), which allows clinicians to visualize the tumor’s location and size.

“In the case of a diagnostic drug, the radioactive isotope gives off gamma radiation which can be detected by a special camera to generate an image that physicians can view. In other words, the diagnostic radiopharmaceutical ‘lights up’ the presence of its biological target, signaling the presence of disease,” said Markison.

The “fight” phase involves therapeutic radiopharmaceuticals delivering beta or alpha particles to cancer cells.

“Most established therapies have employed beta-emitting particles. These particles – such as Lutetium-177 – travel relatively long distances in the body and cause single-stranded DNA breaks to disrupt the growth of the cancerous cells. However, alpha-emitting particles – like those using actinium-225 or lead-212 – emit short-range radiation, but the particles cause double-stranded DNA breaks. The implication of this is that alpha emitters may be better at irrevocably damaging cancer cells without damaging healthy tissue in the vicinity of the tumor,” explained Peter Bak, managing partner at Back Bay Life Science Advisors.

Finally, the “follow” phase allows for tracking disease progression post-treatment. Imaging radiopharmaceuticals can monitor treatment effectiveness, ensuring that remaining cancer cells are identified and addressed. As Suchitra Ghoshal, healthcare research & data analyst at Clarivate explained, “Many radiopharmaceuticals are designed to emit photons that can be imaged using nuclear medicine techniques. This allows for non-invasive visualization of the biodistribution of the therapeutic agent, enabling precise targeting and monitoring of the treatment.”

This complete cycle of treatment and monitoring makes radiopharmaceuticals an effective and versatile approach to precision oncology. Recently, the field has been accelerating not only in terms of investment but also in terms of innovation.

And the field is undergoing rapid advancements, Ghoshal shared what she thinks have been key areas of improvement:

Next-generation radiotracers: Radiotracers are advanced radioactive compounds used in imaging techniques like PET and SPECT to visualize biological processes within the body. These tracers often target specific biomarkers or metabolic pathways associated with diseases, especially cancer. Examples of commercially available radiotracers include fluorodeoxyglucose (FDG), choline, acetate, and fluciclovine. According to Ghoshal numerous companies are actively developing new radiotracers to improve diagnostic accuracy.
Theranostics: The development of theranostic radiopharmaceuticals – which combine diagnostic and therapeutic capabilities in one – represents a dynamic area within nuclear medicine, enhancing personalized treatment approaches. Ghoshal highlighted that the theranostics market is experiencing significant growth, particularly in the treatment of various cancers, including prostate cancer, neuroendocrine tumors, and lymphoma. Theranostic is indeed prone to innovation as Ghoshal pointed out researchers are also investigating the integration of nanotechnology into theranostic radiopharmaceuticals, employing various nanocarriers such as liposomes and dendrimers to improve the delivery and targeting of radionuclides.
Targeted radiopharmaceuticals (TRPs): TRPs are designed to deliver radioactive isotopes specifically to cancer cells or tissues that express certain biomarkers. These agents consist of a targeting molecule, a linker, a chelating agent, and a radionuclide, allowing for precise targeting of tumor cells, similar to how antibody-drug conjugates aim to replace conventional chemotherapy. The primary goal is to maximize the therapeutic effect while minimizing damage to surrounding healthy tissues.
Radiopharmaceuticals in neurodegenerative diseases: TRPs are making their way into neurodegenerative diseases diagnostic. “We are excited about the promise radiopharmaceuticals are showing in neurology, particularly Alzheimer’s disease which has long lacked effective diagnostics,” said Markison.
Artificial intelligence (AI) in radiopharma: Ghostal emphasized one particular method through which AI is particularly contributing to the field – in silico molecular design. “AI enhances the design and validation of radiopharmaceuticals through in silico approaches. These methods utilize computational modeling to predict the behavior of compounds, including their binding properties and pharmacokinetics (absorption, distribution, metabolism, excretion, and toxicity). This predictive capability allows for faster and more cost-effective development processes, reducing the reliance on traditional in vitro and in vivo testing. The integration of AI is expected to significantly expand the capabilities of nuclear medicine.”

What are the challenges yet to be overcome?

It’s not all sunshine and rainbows even in such a dynamic market, some challenges remain, some linked directly to the industry and some regulatory.

Ghoshal pointed out that supply chain management was a significant challenge for the industry. Indeed, efficient production and distribution of radiopharmaceuticals, particularly those with short half-lives, are critical for maintaining a reliable supply chain.

The field also requires specialized infrastructure and a specialized workforce which we are still lacking. “The limited number of trained nuclear medicine physicians and the need for multidisciplinary expertise to administer radiopharmaceuticals effectively hinders widespread adoption,” said Ghoshal.

Let’s not forget the high costs of development and production that might – in the long run – limit the accessibility of radiopharmaceuticals. These technical challenges need to be addressed as well as the regulatory framework.

“A dedicated regulatory framework is necessary due to the unique characteristics of radiopharmaceuticals, including their radioactivity and radiation safety requirements. Radiopharmaceuticals require extensive non-clinical and clinical studies to ensure their safety and efficacy. These studies include non-clinical pharmacology, radiation exposure and effects, and imaging studies,” said Ghoshal.

The framework needs to address the specificities of the field, from the proper disposal of radioactive waste to radiation safety measures. “This includes ensuring the safety of personnel

involved in production and quality control, as well as minimizing radiation exposure to patients during diagnostic procedures and maximizing therapeutic effects while minimizing harm to healthy tissues”, added Ghoshal.

Good manufacturing practices (GMP) have to be strict to ensure the quality and safety of radiopharmaceuticals. This entails adherence to clean room standards and sterility testing, which can be challenging due to radiation safety requirements.

So taking part in the fast-paced radiopharma industry does not come with “no strings attached” and while it is extremely promising, it is equally specific. These challenges did prevent investments, partnerships, and mergers and acquisitions (M&A) from happening in the field, on the contrary.

What have been the most significant radiopharmaceutical deals?

“Radiopharmaceuticals have recently emerged as a hot M&A and licensing target in oncology, reflecting the clinical impact of recently launched radiotherapeutics and the promise of the modality to deliver targeted treatments with improved efficacy and safety versus other types of cancer treatments. For many, the large number of M&A deals in this sector validates the growing interest and potential in radiopharmaceuticals, emphasizing the significant market opportunities available in this field,” said Lantheus’ CEO.

Indeed, the radiopharmaceutical market is very hot at the moment and several deals have had a significant impact on the field. Ghoshal confirms several important deals occurred recently and among them is Blue Earth Diagnostics’ acquisition by Bracco Imaging.

“The acquisition expanded Bracco Imaging’s portfolio in precision medicine and personalized diagnostics. Blue Earth Diagnostics brought novel PET imaging agents, such as Axumin (fluciclovine F 18), which is used for PET imaging in men with suspected recurrent prostate cancer. The combined entity gained access to Blue Earth Diagnostics’ robust pipeline, including PSMA-targeted radiohybrid agents, which have potential applications in both imaging and therapy for prostate cancer,” said Clariviate’s analyst.

Also, Lantheus’ acquisition of the rights to ¹⁷⁷Lu-DOTA-RM2 and⁶⁸Ga-DOTA-RM2 from Life Molecular Imaging, has had a great impact on the market, expanding Lantheus’ product portfolio to include breast cancer, in addition to its existing focus on prostate cancer. This diversification strengthens Lantheus’ position in the market and provides a broader range of therapeutic options for patients.

“Lantheus alone has been involved in multiple deals to acquire assets and full portfolios in the past two years. With our acquisitions of Cerveau Technologies and Meilleur Technologies, we have initiated and strengthened our Alzheimer’s diagnostic portfolio. Additionally, within oncology, we signed a license agreement with Point Biopharma, which was recently acquired by Eli Lilly, for PNT2002 and PNT2003; acquired the global rights to RM2, a novel, clinical-stage radio diagnostic and radiotherapeutic pair from Life Molecular Imaging; and obtained the rights to two pre-clinical assets, an LRRC15 targeting mAb and a TROP2 targeting nanobody from Radiopharm Theranostics,” confirmed Markison.

The deal Lantheus’ CEO mentioned is also one that has allowed the biotech giant, Eli Lilly, to enter the field. “The acquisition aims to leverage Point Biopharma’s expertise in radiolabeling and Eli Lilly’s capabilities in drug development and commercialization. The deal is focused on advancing the development of novel radiopharmaceuticals for cancer diagnosis and treatment and expanding programs PNT2002 and PNT2003 that are in late-stage development for metastatic castration-resistant prostate cancer and neuroendocrine tumors. Respectively, Eli Lilly plans to further develop these therapies and potentially bring several new radioligand therapies to patients with hard-to-treat cancers,” explained Ghoshal.

Lastly, GE Healthcare’s recent agreement with SOFIE Bioscience is expected to have consequences for the promising field of radiopharmaceutical. Under this partnership, GE Healthcare will commercialize and manufacture SOFIE Biosciences’ two investigational fibroblast activation protein inhibitor (FAPI) PET radiotracers for cancer imaging applications. These PET radiotracers are currently undergoing phase 2 clinical trials in the U.S.

“The ability of FAPI tracers to target cancer-associated fibroblasts – a common feature of most tumors – opens doors to new possibilities in cancer imaging. This collaboration allows GE Healthcare to expand its oncology portfolio and leverage SOFIE’s expertise in radiopharmaceutical development and manufacturing. By broadening its product portfolio and strengthening its theranostics capabilities, the collaboration with SOFIE Biosciences will enhance GE Healthcare’s market position in the radiopharmaceuticals market,” added Ghoshal.

What radiopharmaceuticals should you keep an eye on?

The past few years have seen several U.S. Food and Drug Administration (FDA) approvals in the field. Lantheus’ targeted PET imaging agent for prostate cancer, PYLARIFY was approved in 2021 for patients with suspected prostate cancer metastasis and those with suspected recurrence based on elevated serum prostate-specific antigen (PSA) levels.

In 2023, Blue Earth Diagnostics’ POSLUMA for identifying PSMA-positive lesions and high sensitivity for detecting prostate cancer recurrence was approved. In the same year, Telix Pharmaceuticals’ Illucix for patients with metastatic prostate cancer who are candidates for PSMA-directed therapy was also approved.

According to Ghoshal, most of the clinical trials in the radiopharmaceutical segment are focusing on PSMA and FAPI targets. These targets are being explored for their potential in diagnosing and treating various types of cancer, particularly prostate cancer.

Here are some of the trials to keep an eye on:

Additionally, Lantheus has several ongoing candidates to keep an eye on. “In oncology, PNT2002 has shown positive topline results in the SPLASH trial, with additional data expected this year before a potential NDA submission. NAV-4694 (flutafuranol), our late-stage Beta amyloid PET imaging agent for Alzheimer’s disease, is currently in phase 3 development,” said the company’s CEO.

Fusion Pharmaceuticals – recently acquired by AstraZeneca – is also an interesting player in the field with its FPI-2265 (Actinium-225 PSMA therapy) in phase 2/3 for patients with metastatic castration-resistant prostate cancer (mCRPC). FPI-2059 is another Fusion candidate in phase 1 clinical trial. It is a neurotensin receptor 1 (NTSR1) targeted alpha therapy using actinium-225 designed to treat multiple types of solid tumors, including gastrointestinal and pancreatic cancers.

Bayer and Eli Lilly have their own radioligand candidates in clinical trials, after having acquired assets. Bayer’s BAY 3563254 is currently in phase 1 for prostate cancer while Eli Lilly’s PNT 2001 is in phase 2 for the same indication.

Lastly, RayzeBio’s lead candidate RYZ101 – an alpha therapy – is in phase 3 and being tested for patients with neuroendocrine tumors who have previously been treated with lutetium-based somatostatin analog therapies. However, since Bristol Myers Squibb (BMS) acquired the company in February 2024, the trial recruitment has been halted.

What will the radiopharma investment landscape look like in the future?

Looking at the recent deals involving radiopharmaceutical companies and assets – with a mix of specialized players such as Lantheus and more global companies like Eli Lilly entering the market – there’s no doubt the field is very dynamic at the moment. But what can we expect in the years to come?

Indeed, Ghoshal thinks it is this blend that makes the field so promising and prone to fast technological advancements.
“Major pharmaceutical companies are actively acquiring radiopharmaceutical startups to bolster their capabilities in this field. For instance, Novartis’ acquisition of Mariana Oncology expanded its pipeline to include promising radioligand therapies like MC-339 for small-cell lung cancer. Industry players are also forming strategic partnerships to develop novel radiopharmaceuticals. A prime example is the collaboration between Eckert & Ziegler and Alpha-9 Theranostics to secure a supply of Actinium-225, a crucial component for next-generation targeted radionuclide therapies.”

“These trends are expected to accelerate as companies seek to diversify their portfolios. The combination of technological innovation, regulatory approvals, and robust clinical trials will further fuel investment in radiopharmaceutical development and commercialization.”
Suchitra Ghoshal, Healthcare Research & Data Analyst, Medtech Insights at Clarivate

Lantheus’ CEO thinks the coming years will see a wave of next-generation radiopharmaceuticals that aim to improve on each of the three aspects of the technology: Targeting agent, chelator, a molecule securely holding radioactive isotopes, ensuring that the isotope is safely transported to the target site in the body, and isotope to tune the therapeutic index.

“We are investing in next-generation radiopharmaceuticals that we think have the potential to be best in class, offering the potential for powerful new options in diseases like osteosarcoma, prostate cancer, and adenocarcinoma of the lung. We are closely watching the results of ongoing trials in alpha therapeutics from companies like RayzeBio/BMS, Fusion/AstraZeneca, and our own partner, Perspective Therapeutics,” said Markison.

There’s so much happening in the field it’s difficult to keep track but that is a good sign for the future of the field. There is hardly any doubt the field will keep expanding in the future and ultimately bring new solutions to the market, not only for cancer patients but also for neurodegenerative diseases and beyond.