Radiotherapies: Current clinical applications and future directions

While some may associate radiopharmaceuticals with recent innovations, clinical use dates back more than 80 years, with the pioneering application of radioactive iodine for thyroid conditions and cancer.

This early success demonstrated the potential of using radioactive elements to both diagnose and treat disease, setting the stage for the development of the more sophisticated radiopharmaceuticals we’re seeing today.

Recently, there has been significant progress with lutetium-based radiopharmaceuticals such as Lutetium DOTA-TATE and Lutetium PSMA:

• Lutetium-177 (Lu-177) DOTA-TATE: Used primarily for treating neuroendocrine tumors by targeting somatostatin receptors on cancer cells and delivering a high dose of radiation directly to the tumor,
• Lutetium-177 (Lu-177) PSMA: Used for metastatic prostate cancer. It delivers localized radiation by targeting the prostate-specific membrane antigen (PSMA) on cancer cells.

The results are promising and exciting—in one study, 177Lu-PSMA-617 plus standard care significantly prolonged (compared to standard care) both imaging-based progression-free survival and overall survival.

Currently, radiopharmaceutical therapies are typically reserved for patients who have exhausted all other treatment options, such as surgery, hormonal therapy, and chemotherapy. However, these therapies’ success and low toxicity have prompted efforts to integrate them earlier in the treatment process.

Clinical trials are exploring their use after initial surgery, potentially even before chemotherapy or hormonal therapy. The goal is to eventually use radiopharmaceuticals at the earliest stages of cancer diagnosis, reducing the likelihood of recurrence and improving long-term outcomes.

Additionally, combining radiopharmaceuticals with other therapies is being explored to enhance treatment efficacy. For instance, combining external beam radiation with radiopharmaceuticals allows higher radiation doses to be delivered directly to tumors.

Thanks to Lutetium-177, using radiopharmaceuticals for prostate cancer and neuroendocrine tumor treatment remains a primary focus. However, with a properly designed radiopharmaceutical, the sky’s the limit when it comes to types of cancers that could be treated with these drugs.

So, what’s stopping us? At the clinical level, a major barrier is organizational growing pains.

ICYMI: We previously hosted a webinar featuring insights from Kathy Spencer-Pike, Chief Commercial Officer, and Dr Geoff Johnson, Chief Scientific Officer. During the webinar we answered the question “What does Novartis’s pursuit of a label expansion for Pluvicto possibly mean for patients and the field of radiopharmaceutical therapy?”. Part of the webinar was a breakdown of Lutetium-177. Learn what Dr. Johnson had to say.

Overcoming organizational and logistical barriers

The rapid growth of the radiopharmaceutical field has led to “growing pains” as institutions adapt to the increased demand and the complexities of these treatments.

Hospitals and clinics face several challenges in adopting radiopharmaceutical therapies. These include:

• Coordinating care across different medical specialties.
• Ensuring proper training and safety protocols for handling radioactivity.
• Managing financial incentives.

The healthcare infrastructure must adapt to handle the logistical complexities of these treatments, including the need for rapid production and delivery of radiopharmaceuticals. Unlike shelf-stable drugs, radiopharmaceuticals have short half-lives requiring efficient coordination between manufacturing, transportation, and clinical administration.

This ‘melting ice cube’ problem necessitates close coordination and precise timing in the clinical setting. Clinicians must work quickly to prepare and administer these doses. If the right processes are not in place, there is a significant risk that the radiopharmaceutical will decay before it reaches the patient, rendering the dose ineffective.

This requires a seamless integration of production schedules, regulatory compliance, and clinical workflows to ensure patients receive their treatments on time and at the correct dosage.

Additionally, there is a need to expand their use beyond centers of excellence to smaller community hospitals, which treat the majority of cancer patients. Such an expansion is crucial for improving access to care, especially for underrepresented minorities and patients facing financial or logistical challenges.

Ensuring equitable access to these advanced therapies will require concerted efforts to address logistical, financial, and regulatory challenges.

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What do you think are the biggest challenges or opportunities for expanding access to radiopharmaceuticals in healthcare? Let us know in the comments. ??

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