In recent decades, radiopharmaceuticals have undergone significant transformations. Initially, these drugs were primarily used for imaging to facilitate the early diagnosis of cancer and other diseases. With the integration of treatment and diagnostic technologies, the development of radiopharmaceuticals has radically changed this field.
Radiopharmaceuticals that combine diagnostics and therapeutics can detect and treat diseases, providing a more personalized approach to medicine. As Lantheus CEO Brian Markison pointed out, “Radiopharmaceuticals can discover, combat, and track. These drugs have the unique ability to target specific cancer cells, offering diagnostic imaging while delivering targeted therapeutic radiation to destroy cancer cells.”
The radiopharmaceutical market is experiencing exponential growth. A Statista market research report indicates that the value of the radiopharmaceutical field is expected to reach $14 billion by 2032, up from nearly $7 billion currently. “This growth will be driven by innovations in diagnostic and therapeutic radiopharmaceuticals, an increase in the number of patients receiving treatment, and the expanding applications of these technologies in various cancers and neurology,” Markison added.
Radiopharmaceuticals are becoming a powerful form of precision medicine that can “discover,” “combat,” and “track” cancer cells. Radiopharmaceuticals include a targeting agent that combines radioactive isotopes with specific biological targets on cancer cells. This combination can accurately deliver radiation to tumors while minimizing damage to surrounding healthy tissues. This approach enables the drugs to seek out cancer cells, destroy them with targeted radiation, and track the effectiveness of treatment.
In the “discover” phase, radiopharmaceuticals bind to tumor-specific antigens or receptors, such as prostate-specific membrane antigen (PSMA), used in the treatment of prostate cancer. The attached radioactive isotopes emit gamma rays, which can be detected using imaging techniques such as PET (Positron Emission Tomography) or SPECT (Single Photon Emission Computed Tomography), allowing clinicians to visualize the location and size of the tumor.
The “combat” phase involves the delivery of beta or alpha particles to cancer cells for radiotherapy.
“Most established therapies use beta-emitting particles. These particles, like lutetium-177, have a relatively long range within the body and cause single-strand DNA breaks, thereby disrupting cancer cell growth,” explained Peter Bak, managing partner at Back Bay Life Science Advisors.
Alpha particles (such as those emitted by actinium-225 or lead-212) can cause short-range radiation, leading to double-strand DNA breaks. This means that alpha radiation irreversibly damages cancer cells without harming healthy tissues near the tumor.
In the “track” phase, radiopharmaceutical imaging can monitor treatment effectiveness, ensuring that remaining cancer cells are identified and addressed. “Many radiopharmaceuticals can be imaged using nuclear medicine technologies, allowing for precise targeting and monitoring of treatment,” said Suchitra Ghoshal, healthcare research and data analyst at Clarivate.
This complete cycle of treatment and monitoring makes radiopharmaceuticals an effective and universal approach in precision oncology. Recently, both investment and innovation in this field have accelerated.
Ghoshal shared several key areas that need improvement:
Ghoshal pointed out that supply chain management is a significant challenge facing nuclear medicine. Indeed, maintaining a reliable supply chain is crucial for the efficient production and distribution of radiopharmaceuticals, especially those with short half-lives.
The field also requires specialized infrastructure and currently lacks skilled professionals. Ghoshal stated, “The number of trained nuclear medicine physicians is limited, and we need multidisciplinary expertise to effectively manage radiopharmaceuticals, which hinders their widespread application.”
The high costs of development and production may restrict the accessibility of radiopharmaceuticals in the long term. In addition to technological challenges, regulatory issues also need to be addressed.
“Given the uniqueness of radiopharmaceuticals, including their radioactive and radiation safety requirements, it is necessary to establish a dedicated regulatory framework. Radiopharmaceuticals require extensive non-clinical and clinical studies to ensure their safety and efficacy,” Ghoshal added.
These studies include non-clinical pharmacology, radiation exposure and effects, and imaging studies, as well as ensuring personnel safety during production and quality control, minimizing radiation exposure to patients during diagnosis, and maximizing therapeutic effects while minimizing damage to healthy tissues.
Therefore, the challenges facing the rapidly developing radiopharmaceutical industry do hinder investment, collaboration, and mergers and acquisitions in the field.
The radiopharmaceutical market is currently booming, with several transactions significantly impacting the field, including the acquisition of Bracco Imaging by Blue Earth Diagnostics.
This acquisition expands Bracco Imaging's portfolio in precision medicine and personalized diagnostics. Blue Earth Diagnostics brings new PET imaging agents such as Axumin (fluciclovine F 18) for PET imaging in suspected recurrent prostate cancer patients.
Additionally, Lantheus acquired rights to 177Lu-DOTA-RM2 and 68Ga-DOTA-RM2 from Life Molecular Imaging, expanding Lantheus's portfolio to include indications for breast cancer in addition to prostate cancer treatment. This not only strengthens Lantheus's market position but also offers patients a broader range of treatment options.
In October of last year, an agreement between GE Healthcare and SOFIE Biosciences is expected to have a significant impact on the radiopharmaceutical field. According to the collaboration agreement, GE Healthcare will commercialize and produce two investigational fibroblast activation protein inhibitor (FAPI) PET imaging agents for cancer imaging applications developed by SOFIE Biosciences.
FAP is an enzyme highly expressed in cancer-associated fibroblasts (CAFs), which are key components of the tumor microenvironment that support the growth and spread of cancer cells. As CAFs are present in most tumor types, including breast, pancreas, colon, lung, liver, and stomach, FAP-targeted diagnostics hold enormous potential in tumors as well as other diseases, including inflammation, fibrosis, and arthritis.
These PET radiotracers are currently undergoing Phase II clinical trials in the United States.
In recent years, the FDA has approved several products in this field. For example, Lantheus's targeted PET imaging agent PYLARIFY was approved in 2021 for suspected metastatic prostate cancer patients and suspected recurrent patients based on elevated serum prostate-specific antigen (PSA) levels.
In 2023, Blue Earth Diagnostics' highly sensitive POSLUMA for identifying PSMA-positive lesions and detecting recurrent prostate cancer was approved. The same year, Telix Pharmaceuticals' Illucix was also approved for patients with metastatic castration-resistant prostate cancer suitable for targeted PSMA radioligand therapy Pluvicto.
Ghoshal indicated that most clinical trials in the field of radiopharmaceuticals are focused on PSMA and FAPI targets.
Here are some notable trials:
Additionally, Lantheus has several noteworthy candidates in oncology: PNT2002 has shown positive top-line results in the SPLASH trial, with more data expected to be disclosed this year; the advanced beta amyloid PET imaging agent NAV-4694 for Alzheimer's disease is currently in Phase III development.
Fusion Pharmaceuticals, acquired by AstraZeneca, is also a player in the field, with its therapy FPI-2265 for patients with metastatic castration-resistant prostate cancer currently in Phase II/III clinical trials. FPI-2059 is another candidate in Phase I clinical trials, which is an NTSR1-targeting alpha therapy using actinium-225, aimed at treating various types of solid tumors, including gastrointestinal and pancreatic cancers.
Large pharmaceutical companies are actively acquiring radiopharmaceutical startups to enhance their capabilities in this field.
In May 2024, Novartis announced the acquisition of Mariana Oncology. This acquisition covers a robust RLT project portfolio involving a range of solid tumor indications (such as breast cancer, prostate cancer, and lung cancer), including an actinium-based lead RLT project MC-339 targeting small cell lung cancer.
Many companies are also choosing to establish strategic partnerships to develop new radiopharmaceuticals. A major example is the collaboration between Eckert & Ziegler and Alpha-9 Theranostics to ensure the supply of actinium-225, a key component of next-generation targeted radioligand therapies.
The CEO of Lantheus believes that a wave of next-generation radiopharmaceuticals will emerge in the coming years, improving targeted formulations, chelators, and molecules for safely holding radioactive isotopes, ensuring isotopes are safely transported to target sites in the body, and adjusting the therapeutic index of isotopes.
There is no doubt that nuclear medicine will continue to evolve in the future, bringing more new treatment options to the market, starting with cancer and expanding to more other diseases such as neurodegenerative diseases.
