Researchers at the Australian Nuclear Science and Technology Organisation have developed a radiopharmaceutical treatment for advanced prostate cancer that delivers therapeutic radiation directly to cancer cells throughout the body while sparing healthy tissue.

The treatment uses lutetium-177 bound to a molecule that specifically targets prostate-specific membrane antigen, a protein expressed on prostate cancer cells. When injected, the radiopharmaceutical travels through the bloodstream and binds to cancer cells wherever they exist, including metastases in bones and other organs.

The lu tetium-177 then delivers localised radiation that kills cancer cells while leaving surrounding healthy tissue largely unaffected. Clinical trials show the treatment extends survival and reduces cancer-related symptoms for men with metastatic prostate cancer that no longer responds to standard treatments.

Prostate Cancer Challenge

Prostate cancer is the most commonly diagnosed cancer in Australian men, with about 24,000 new cases annually. Most cases respond well to surgery, radiation, or hormone therapy. But some cancers become resistant to these treatments and spread to other parts of the body.

Metastatic castration-resistant prostate cancer, the term for advanced disease that no longer responds to hormone therapy, has limited treatment options. Chemotherapy provides some benefit but comes with significant side effects. Survival after reaching this stage typically measures in months to a few years.

Treatments that can target cancer cells throughout the body while minimising damage to healthy tissue are desperately needed. Radiopharmaceuticals offer this capability by combining a cancer-targeting molecule with a radioactive isotope that kills cells it contacts.

Dr Sarah Thompson, who leads ANSTO’s radiopharmaceutical research, said prostate cancer is particularly suitable for this approach because prostate-specific membrane antigen provides an excellent target. The protein is highly expressed on cancer cells but has limited presence in healthy tissue.

Development Process

ANSTO has unique capabilities in Australia for producing medical radioisotopes. The organisation operates nuclear reactors and accelerators that create isotopes used in diagnostic imaging and therapy. Lutetium-177 production uses one of these reactors.

The researchers combined lutetium-177 with a targeting molecule called PSMA-617, which binds strongly to prostate-specific membrane antigen. This combination has been investigated internationally, but ANSTO developed improved production methods and quality control processes suited to Australian regulatory requirements and clinical needs.

Producing radiopharmaceuticals requires meticulous attention to quality because the products are injected directly into patients. Any impurities or contamination could cause serious harm. ANSTO’s production facilities meet stringent good manufacturing practice standards for pharmaceutical production.

Clinical trials testing the ANSTO-produced radiopharmaceutical enrolled 150 men with metastatic castration-resistant prostate cancer at hospitals in Sydney, Melbourne, and Perth. Patients received treatments every six weeks for up to six cycles, with careful monitoring for efficacy and side effects.

Results showed that about 65% of patients experienced significant reduction in cancer-related symptoms. Median survival increased by approximately eight months compared to standard care. Side effects were generally manageable, primarily temporary reductions in blood counts requiring monitoring but rarely stopping treatment.

Comparison to Other Treatments

Several other radiopharmaceuticals for metastatic prostate cancer exist or are in development. Radium-223 is approved for bone metastases specifically. Actinium-225 PSMA therapy is being investigated and shows promise but faces production challenges because actinium-225 is scarcer than lutetium-177.

Lutetium-177 PSMA therapy balances efficacy, safety, and production feasibility better than many alternatives. The radiation emitted by lutetium-177 has a range of about 2 millimetres in tissue, long enough to kill cancer cells but short enough to limit damage to adjacent healthy tissue.

International trials of similar lutetium-177 PSMA treatments have reported comparable results to ANSTO’s trials, validating the approach across different patient populations. Some patients benefit dramatically with complete or near-complete cancer responses, while others see modest benefit.

Predicting which patients will respond best remains challenging. Some research suggests that patients with higher PSMA expression on imaging scans respond better, which makes biological sense. ANSTO researchers are investigating whether screening scans can identify patients most likely to benefit.

Production and Supply

ANSTO is scaling up production to meet Australian clinical demand. The organisation can currently produce enough lutetium-177 PSMA for about 1,000 treatment courses annually. Demand is expected to reach 2,000-3,000 treatments per year as use expands.

The production capacity depends on reactor operating time, processing capability, and quality control throughput. ANSTO is investing in equipment upgrades to increase capacity, funded partly by federal government capital allocations and partly by revenue from radiopharmaceutical sales.

There’s also export potential. Several countries in the Asia-Pacific region lack domestic radioisotope production capability and import from Australia or Europe. ANSTO already exports other medical radioisotopes and could expand exports to include lutetium-177 PSMA.

However, radioisotope exports face logistical challenges. Lutetium-177 has an 6.6-day half-life, meaning it decays relatively quickly. Production must be timed to account for transport duration so product arrives with adequate activity for use. This limits export distances and requires careful logistics coordination.

Domestic production provides Australia with supply security for an important cancer treatment. Global radioisotope supply has experienced disruptions when overseas production facilities have maintenance or technical problems. Domestic capability reduces dependence on international supply chains.

Regulatory Approval

The Therapeutic Goods Administration has granted provisional approval for ANSTO’s lutetium-177 PSMA treatment based on clinical trial results. Provisional approval allows use while additional data continues accumulating. Full approval will follow pending completion of long-term follow-up studies.

Provisional approval enables access for patients who have exhausted other treatment options. Oncologists can prescribe the treatment for appropriate patients, with costs covered through special access schemes until Medicare listing is finalised.

Medicare listing is under consideration by the Pharmaceutical Benefits Advisory Committee, which assesses cost-effectiveness of treatments for government subsidy. The radiopharmaceutical would typically cost $15,000-20,000 per treatment course without subsidy, unaffordable for most patients.

International regulatory approvals are also progressing. The US FDA and European Medicines Agency are reviewing similar lutetium-177 PSMA treatments, with approvals likely in coming years. International approval would open export markets and provide validation of the approach.

Clinical Implementation

Rolling out new cancer treatments requires training oncologists and nuclear medicine physicians in appropriate patient selection, treatment protocols, and side effect management. ANSTO has partnered with major cancer centres to establish treatment protocols and train clinical staff.

Not all hospitals have nuclear medicine facilities capable of administering radiopharmaceuticals. The treatments require lead-shielded rooms for patient safety and staff radiation protection. Radioactive waste handling and patient discharge procedures must follow nuclear safety regulations.

Major metropolitan cancer centres generally have appropriate facilities, but regional centres often don’t. This creates access issues for patients outside capital cities. Some solutions include transporting patients to major centres for treatment or establishing radiopharmaceutical treatment capabilities at larger regional hospitals.

Patient selection is critical. The treatment works only for cancers that express PSMA, which must be confirmed through diagnostic imaging. Patients with good kidney function and adequate blood counts are suitable, while those with severe kidney disease or low blood counts may not tolerate treatment safely.

Research Directions

ANSTO researchers are investigating additional applications for radiopharmaceutical therapy beyond prostate cancer. Some other cancers express targetable proteins that could be addressed with similar approaches. Neuroendocrine tumours and certain lymphomas are being studied.

There’s also work on combination approaches. Using radiopharmaceuticals together with immunotherapy or other treatments might produce better results than either alone. Understanding how to optimally combine treatments requires clinical trials.

Improved targeting molecules that bind more specifically to cancer cells while avoiding healthy tissue could further improve the therapeutic window. ANSTO collaborates with medicinal chemistry groups at Australian universities on next-generation targeting molecules.

Alternative radioisotopes with different radiation characteristics might suit different clinical situations. ANSTO is developing capabilities to produce additional therapeutic isotopes, expanding the radiopharmaceutical toolbox available for cancer treatment.

Impact on Prostate Cancer Care

For men with advanced prostate cancer, lutetium-177 PSMA therapy provides a valuable additional treatment option. It won’t cure metastatic disease, but it can extend survival and improve quality of life during a difficult stage of illness.

The treatment’s relatively mild side effects compared to chemotherapy make it particularly attractive. Many patients can continue normal activities during treatment, which isn’t always possible with intensive chemotherapy.

Oncologists are still determining the optimal place for radiopharmaceutical therapy in prostate cancer treatment sequences. Should it be used immediately when hormone therapy fails, or reserved for later when other options are exhausted? Clinical trials addressing these questions are ongoing.

There’s hope that using the treatment earlier in disease progression, when tumour burden is lower, might produce better outcomes. But this needs validation through trials comparing different treatment sequences.

The development represents Australian research and industry capability in advanced medical technology. From radioisotope production through clinical trials to commercial deployment, ANSTO and partner institutions demonstrated the complete pathway for bringing sophisticated cancer treatments to patients.