Attacking cancer targets with radiotherapy

Therapeutic radioisotopes can be designed to target cancer cells, delivering radiation precisely while leaving surrounding healthy cells intact. In this Innovation Spotlight, John BabichCo-founder, President, and Chief Scientific Officer of Ratio Therapeutics discusses how radiopharmaceuticals are constructed for optimal cancer targeting and treatment.

What are radiopharmaceuticals and what role do they play in cancer treatment?

Radiopharmaceuticals are drugs that combine molecules and radioactive isotopes to target specific cells, such as cancer cells. Cancer treatment involves delivering targeted radiation directly to the tumor, minimizing damage to healthy tissue. This precision improves treatment efficacy, especially for cancers that are difficult to treat with traditional methods. Radiopharmaceuticals can be used in the diagnosis and treatment of cancer, providing a dual approach that improves the accuracy of tumor detection and becomes a powerful tool for destroying tumors, especially for metastatic and late-stage disease. Masu.

How are radiopharmaceuticals different from other cancer treatments?What problems are radiopharmaceuticals trying to solve?

Many conventional cancer treatments, such as chemotherapy, have limitations because they attack both healthy and cancer cells indiscriminately, causing serious side effects. External radiation therapy is effective for localized disease. Therapeutic radiopharmaceuticals are administered systemically, so they can deliver radiation to cancer that has spread throughout the body. Precise targeting of radiopharmaceuticals to cancer cells minimizes off-target localization in normal tissues, thereby minimizing adverse effects on these tissues. This precise targeting reduces toxicity and increases efficacy, especially against a wide range of metastatic tumors. Additionally, radiopharmaceuticals can help researchers visualize and treat cancer, depending on the radioactive isotope used to prepare the radiopharmaceutical. This allows for more customized solutions for patients who are resistant to traditional treatments.

Can you give me an example of how radiopharmaceuticals work?

Radiopharmaceuticals work like a locksmith who uses special keys to unlock specific doors. Cancer cells are like a locked door, and traditional treatments are like using a crowbar, which can open any door but damages the door frame and surrounding area. . But radiopharmaceuticals are special keys designed to fit just the lock on cancer cells. Interaction with specific receptors on these cells allows selective delivery of targeted radiation, effectively opening the door to therapy while preserving the integrity of nearby healthy cells. Masu. This precision increases the effectiveness of cancer treatment and minimizes collateral damage.

How do scientists keep radiopharmaceuticals stable until they reach their destination?

Typical components of radiopharmaceuticals that are important to successfully reach the target are the targeting moiety, linker, chelating agent, and radioactive isotope. Ideally, the radioactive isotope is combined with a suitable chelating agent (usually a metal) that binds tightly to it. Chelating agents are chemically attached to the targeting moiety via a linker. This complex structure of ligand, linker, chelator, and isotope ensures that the radiopharmaceutical reaches its target on cancer cells intact. Additionally, radiopharmaceuticals are prepared in formulation matrices that maintain chemical stability during manufacturing and transportation.

How do scientists choose which radioisotopes to use? And what are the advantages of alpha and beta radiation?

The choice of radioisotope depends on the therapeutic needs, including the type of cancer and treatment goals. Scientists evaluate factors such as the half-life of the isotope, the type of radiation, the potential radiation energy delivered, and the range. Alpha-emitting isotopes deliver high-energy radiation over a very short distance, making them ideal for targeting small, localized tumors with minimal impact on surrounding healthy tissue. In contrast, beta-emitting isotopes emit lower-energy radiation over longer distances, making them more suitable for treating larger or more diffuse tumors. Each isotope type offers unique benefits tailored to the specific characteristics of the cancer being treated.

How can the design of structural motifs be optimized for target type, location, and delivery needs?

The design of structural motifs for radiopharmaceuticals can be optimized by focusing on target affinity, pharmacokinetics, and delivery efficiency. With this in mind, we designed a platform named Trillium. This allows radiotherapy drugs to bind to albumin, thereby enhancing circulation throughout the body and improving tumor delivery. Tuning the plasma retention curve by adjusting reversible binding to albumin allows the radiopharmaceutical to remain in circulation longer for more precise tumor targeting.

How can radiopharmaceuticals be combined with other cancer treatments?

When combined with immunotherapy, radiopharmaceuticals deliver radiation directly to the tumor, damaging cancer cells and making them more visible to the immune system. This makes the cancer more susceptible to immune attack and increases the effectiveness of treatments such as immune checkpoint inhibitors. In addition, damaged cell debris can create an inflammatory environment that increases the immune response, helping immunotherapies to penetrate tumors and work more effectively. This combination provides a synergistic approach, maximizing the strengths of both treatments to better control cancer.

What excites you most about the future of radiopharmaceuticals?

From a technical point of view, radiotherapy has the potential to become an essential component of cancer treatment, especially as an adjuvant. Advances are likely to be made in the use of preoperative radiotherapy and immunotherapy to enhance treatment efficacy. This includes translating preclinical research into clinical practice, where targeted radiopharmaceuticals can play an important role in disease management. Combining this technology with other approaches will provide new and personalized ways to treat cancer, ultimately improving patient care and outcomes.