Radiopharmaceuticals: Revolutionizing Precision Medicine

In the last two decades, cancer treatment has witnessed significant advancements. However, traditional treatments such as surgery, chemotherapy, and radiation therapy continue to be at the forefront of cancer management. Radiation therapy, in particular, has been employed for over a century, primarily utilizing external beams of radiation to eliminate tumors. Although effective, this approach causes collateral damage to surrounding healthy tissues, resulting in various side effects. To address these challenges, scientists have been exploring a new class of drugs called radiopharmaceuticals, which deliver radiation therapy directly to cancer cells.?

Studies show that this targeted approach can minimize side effects while effectively eliminating even tiny cancer cell deposits. Experts believe that radiopharmaceuticals will revolutionize radiation oncology in the years to come. In this blog post, we will delve into the concept of radiopharmaceutical therapeutics, their benefits, and how they represent a significant milestone in the field of precision cancer treatment.

Understanding Radiopharmaceuticals

Radiopharmaceuticals consist of three main building blocks: a radioactive molecule, a targeting molecule (that recognizes and latches specifically onto cancer cells), and a linker that joins the two together. Such compounds can be injected, infused, inhaled, or ingested, and then make their way into the bloodstream.?

The concept of combining a cancer-targeting molecule with a molecule that eliminates cancer cells is not new. For example, several drugs called antibody–drug conjugates, in which an antibody that binds to specific cancer cells is linked to a toxic drug, have been approved for treating cancer. However, toxic payloads of ADC’s need to first be absorbed into cancer cells and remain there long enough to cause damage.?

Radiopharmaceuticals, on the other hand, can still do damage by simply binding to the cancer cell. Plus, depending on the specific radioactive compound utilized, the energy generated can penetrate not only the targeted cancer cell but also approximately 10 to 30 surrounding cancer cells. This broadens the reach of a single radiopharmaceutical molecule, enabling the elimination of a greater number of cancer cells.

Researchers are currently developing and evaluating radiopharmaceuticals for various types of cancers, including melanoma, lung cancer, colorectal cancer, liver cancer, leukemia, and rare cancers called gastroenteropancreatic neuroendocrine tumors. Experts say that any tumor with a targetable molecule on its cell surface combined with a well-functioning blood supply, capable of delivering drugs, has the potential to be treated with radiopharmaceuticals.

Theranostics

Many radiopharmaceuticals are re-engineered versions of existing compounds used for nuclear imaging (i.e. PET scans). PET imaging tests use weak radioactive compounds linked to molecules that bind to cancer cells, allowing specialized cameras to see where cancer has spread throughout the body. Researchers have now repurposed these targeting molecules to now carry potent radioactive isotopes that can kill cancer cells rather than simply make them visible.?

This means that radiopharmaceuticals have the unique advantage of being both diagnostic and therapeutic. This strategy is known as theranostics. Theranostics is the term used to describe the combination of using one radioactive drug to identify where the cancer is located in the body (diagnose) and a second radioactive drug to deliver therapy to treat the main tumor and any metastatic tumors.?

These therapeutic drugs bind to the specified target protein on the tumor cell membrane, allowing the drug to enter the tumor cells and kill it by damaging that cell’s DNA. Healthy cells around the tumor that do not have the target protein on their membrane are not affected by the drug. That’s how radiopharmaceuticals are able to spare the healthy tissues surrounding cancer.?

The development of diagnostics working hand-in-hand with therapeutics has made the field of radiopharmaceuticals that much more exciting. These theranostic drugs will enable doctors to personalize treatment based on the very specific type of cancer and the specific tumor cell membrane proteins that each patient may have. The cancers most commonly treated with theranostics are thyroid cancer, prostate cancer, and neuroendocrine cancers. But in theory, it can be used against all kinds, provided scientists can identify good targets on cancer cells.

Alpha vs. Beta?

A crucial decision when developing radiopharmaceuticals is deciding which type of radiation you will use to kill tumor cells; alpha or beta. The choice between beta-emitting and alpha-emitting radiation depends on the specific therapeutic goals and characteristics of the targeted cells. Beta-emitting radionuclides can penetrate deeper into tissues, allowing them to treat larger tumors or tumors located further from the surface. They deliver radiation to tumor cells and nearby tissues, affecting a broader area. Beta particles cause damage to the DNA of the targeted cells, leading to cell death.

In contrast, alpha-emitting radiation has a shorter range of penetration, which makes it highly suitable for targeting small clusters of cancer cells or micrometastases. Alpha-emitting radionuclides, such as actinium-225 (Ac-225) or radium-223 (Ra-223), are utilized in certain targeted alpha therapy (TAT) approaches. Alpha particles, such as deliver a highly concentrated and potent dose of radiation within a limited distance. This localized effect can be advantageous for treating microscopic cancer cell clusters while minimizing damage to surrounding healthy tissues. Alpha particles deposit a significant amount of energy per unit length traveled, resulting in more severe DNA damage and increased effectiveness in killing cancer cells.

Two radiotherapeutics that are currently approved by the FDA and EMA are Novartis’, Pluvicto and Lutathera, which treat prostate cancer and certain digestive tract cancers. These radiopharmaceuticals both rely on beta-emitting particles. Despite the success of beta-emitters in cancer therapeutics, many radiopharma biotechs are turning their attention to alpha-emitting radionuclides, since they are shown to be more effective in killing cancer cells while reducing toxic damage outside the tumor region.

For example, one such biotech company that is utilizing alpha-emitting radionuclides to develop targeted radiopharmaceuticals is San Diego based, RayzeBio. They’re sending the highly potent alpha emitting radioisotope, Actinium-225, to kill cancer cells in neuroendocrine tumors and small cell lung cancer. Actinium-225 has high energy density acting at distances of just a few cell widths, restricting the radiation to the cancer cells of interest while sparing nearby healthy tissue.??

Production and Distribution Challenges

Manufacturing:

• Radioisotope production - Radiopharmaceuticals rely on the availability of radioisotopes, which are typically produced in specialized nuclear reactors or cyclotrons. These facilities require strict operational controls and highly trained personnel.
• Quality control - Rigorous quality control measures are crucial to ensure the safety, efficacy, and purity of radiopharmaceuticals. This involves testing for radiochemical purity, radionuclide identity, and specific activity.

Distribution and Logistics:

• Radioactive material handling - Radiopharmaceuticals require specialized handling and packaging due to their radioactive nature. Proper shielding, containment, and compliance with radiation safety regulations are necessary throughout the distribution process.
• Timely delivery - Radiopharmaceuticals have limited shelf lives due to the decay of the radioisotopes. Ensuring timely delivery is critical to maintaining the product's potency and efficacy.

Regulatory Compliance:

• Regulatory approvals - Radiopharmaceuticals must undergo regulatory scrutiny and obtain necessary approvals before being marketed and distributed. This involves demonstrating safety, efficacy, quality control, and adherence to Good Manufacturing Practices (GMP).
• Licensing and permits - Facilities involved in the production, storage, and distribution of radiopharmaceuticals require appropriate licenses and permits. Compliance with radiation safety regulations is essential.

Conclusion

Radiopharmaceuticals represent a groundbreaking advancement in cancer treatment, enabling the targeted delivery of radiation therapy to cancer cells. By minimizing collateral damage and increasing precision, radiopharmaceuticals offer the potential for more effective and personalized cancer therapies. With ongoing research and clinical trials, the field of radiopharmaceuticals continues to expand, providing hope for improved outcomes in the battle against cancer. Despite the production and distribution setbacks, the sector is one that will continue to grow and holds promise for transforming the landscape of cancer treatment in the coming years.

Stay tuned for Part 2 of our Radiopharmaceuticals 3 Part Series! In our next blog we will be discussing the current radiopharmaceutical industry landscape: market size and growth, key players and trends, advancements and future direction.?

All sources are linked within this post.