Advanced Metastatic Prostate Cancer Treatment: Comparing Lutetium-177 — Actinium-225 — Radium-223 Therapies
Therapeutic radionuclides Lutetium-177-PSMA, Actinium-225-PSMA, and Radium-223 have been successfully used in the treatment of advanced prostate cancer. These are modern drugs, in the development of which scientists have corrected the shortcomings of earlier used isotopes. With Actinium-225 emerging as a promising alternative to Lutetium-177 and Radium-223 as a relatively new drug, it is crucial to understand the benefits, indications, and potential side effects of each treatment modality.
Indications for the use of Lutetium-177, Actinium-225, and Radium-223
Differences in the action of radionuclides are caused by two main parameters:
- The physical characteristics of the radionuclide in its composition are the type of radiation, the radiation radius of the surrounding tissues, and the half-life
- The characteristics of the radionuclide carrier molecule are the reliability and accuracy of its binding to tumor receptors
| Radionuclide | Indications for use | The principle of therapeutic action |
|---|---|---|
| Lutetium-177-PSMA Beta radiation (high-energy electrons), half-life – 6.5 days | Metastatic castration-resistant prostate cancer, in particular with bone metastases | Lutetium-177 was the first radionuclide to receive FDA approval for use in prostate cancer treatment. The carrier molecule in this drug is PSMA, a prostate-specific membrane antigen. PSMA receptors on the surface of cancer cells serve as a unique target, to which a therapeutic radionuclide binds after its intravenous administration. The radiation of Lutetium-177-PSMA extends to no more than 100-200 surrounding cells. |
| Actinium-225-PSMA Alpha radiation (helium nuclei), half-life – 10 days | Metastatic castration-resistant prostate cancer, in particular with bone metastases | For the treatment of metastatic prostate cancer, Actinium-225 binds to the same molecular carrier as Lutetium-177 – PSMA. The mechanism of action of the drug differs due to the replacement of the isotope: the action of Actinium-225 lasts 4 days longer, and the radius of action is limited to 1-2 surrounding cells. Due to this, Actinium-225 therapy is effective even in the absence of a satisfactory response to Lutetium-177. |
| Lutetium-177-DOTATATE Beta radiation (high-energy electrons), half-life – 6.5 days | Neuroendocrine prostate cancer (NEPC) | In this case, the radioisotope Lutetium-177 binds to another carrier substance, namely the DOTATATE molecule. DOTATATE has a structural affinity for somatostatin receptors, which are abundant on the surface of neuroendocrine tumors. After intravenous administration, Lutetium-177-DOTATATE accumulates in neuroendocrine tumors of the prostate and destroys them, preserving the normal function of the bladder and intestines. |
| Radium-223 Natural alpha radiation (helium nuclei), half-life – 11.5 days | Metastatic castration-resistant prostate cancer, in particular with bone metastases | In structure, radium is similar to calcium, which is the main structural element of bone tissue. Thanks to this, it integrates into the natural bone metabolism and specifically irradiates actively multiplying cells of bone metastases of prostate cancer. The alpha radiation of Radium-223 acts within 2-10 surrounding cells, and the drug, which is not absorbed by the bones, is quickly excreted through the intestines. According to data from clinical studies, when using the drug, malignant cells receive 8-9 times more radiation compared to healthy tissues. |
Lutetium-177-PSMA-617 was approved by the FDA (Food and Drug Administration) for the treatment of castration-resistant metastatic prostate cancer in summer of 2021. Clinical trials are also being conducted on Lutetium treatment in the earlier stages of prostate cancer. To date, indications for the use of Lutetium-177-PSMA-617 are as follows:
- Metastatic prostate cancer with metastases in the bones, lymph nodes, and lungs
- Failure to respond to hormone therapy and chemotherapy
- Contraindications to hormone therapy and chemotherapy
- Sufficient number of PSMA receptors based on preliminary PSMA PET/CT with Gallium-68
Another modification of the isotope Lutetium-177, namely Lutetium-177-DOTATATE, is intended for patients with rare neuroendocrine prostate cancer (NEPC). Four cycles of treatment with Lutetium-177-DOTATATE, with an interval of 8 weeks between procedures, are prescribed in cases with:
- Contraindications to surgery or chemotherapy
- Ineffectiveness of previous surgery or chemotherapy
- Failure to accurately determine the characteristics of the primary tumor, the presence and number of metastases
Actinium-225-PSMA is an alternative treatment carried out under similar conditions. It is also frequently administered after the ineffectiveness of 1-2 courses of treatment with Lutetium-177-PSMA. The versatility of Actinium-225 PSMA cancer treatment is clinically significant, offering multiple integration points in the personalized treatment. Oncologists may administer Actinium-225 pre- or post-Lutetium-177 therapy, as a direct alternative, or in select cases, before chemotherapy initiation. This flexibility in treatment sequencing, combined with its high linear energy transfer and short tissue penetration range, positions Actinium-225 as a valuable innovative cancer treatment in the evolving paradigm of advanced prostate cancer targeted therapy.
Radium-223 was developed by Bayer, primarily for the treatment of bone metastases in advanced prostate cancer. Bone metastases of prostate tumors activate osteoblasts, which are cells with intensive metabolisms responsible for building bones. Osteoblasts actively accumulate calcium ions, due to the structural similarity with which radioactive Radium-223 penetrates into metastases. This makes Radium-223 the drug of choice for:
- Confirmed metastatic prostate cancer with osteoblastic bone metastases
- Absence (or a small number) of metastases in internal organs (lymph nodes, liver, and lungs)
In addition to treatment, radionuclides are also actively used in the diagnosis of prostate cancer. For example, diagnostic examination by means of radionuclides typically includes imaging with Gallium-68-DOTATATE (neuroendocrine prostate cancer) and PSMA PET/CT with Gallium-68 (prostate cancer).
What is the effectiveness of the drugs?
The effectiveness of treatment with radiopharmaceuticals depends on a number of factors:
- Disease characteristics
- Previous treatment strategy and treatment response
- Radiopharmaceutical agent
- Duration of treatment and its combination with standard options
Lutetium-177-PSMA
Several clinical trials explored clinical efficacy of Lutetium-177, Actinium-225, and Radium-223. According to the results of the VISION clinical trial, Lutetium-177-PSMA received FDA approval and the status of "breakthrough therapy" for metastatic hormone-resistant prostate cancer in 2021. After 1 or several courses of treatment with Lutetium-177-PSMA, the 5-year survival rate of patients with metastatic prostate cancer increased to 30%. The risk of disease recurrence also decreased; in 30-40% of patients, remission persisted for 2 years.
Actinium-225-PSMA
The trials on Actinium-225 PSMA as a more innovative pharmaceutical are still ongoing, but the results obtained so far show a 50-80% decrease in the number of metastases and a 90% decrease in PSA levels in 82% of men. A recent large-scale study, known as the WARMTH Act (Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer, mCRPC), has shown encouraging results for men with advanced prostate cancer.
Actinium-225 vs Lutetium-177
There is an ongoing dispute about clinical superiority and specific indications for Actinium-225 and Lutetium-177. Since Actinium-225 PSMA binds more strongly to tumor receptors, and its half-life is 60% longer than the half-life of Lutetium-177, it ensures a more prolonged therapeutic effect in Lutetium-177 vs Actinium-225 clinical efficacy debates. The radius of action is only 1-2 cells (as opposed to 100-200 cells for Lutetium-177), which also helps to protect healthy tissues. Therefore, in a Lutetium-177 vs Actinium-225 debate, the latter demonstrates potential superiority over the current standard Lutetium-177.
Radium-223
Radium-223 was studied in the ALSYMPCA clinical trial in 921 men. According to the results of the trial, the drug increased the average overall survival by 3.6 months, reduced the risk of death by 30% and significantly reduced the risk of developing pathological spinal fractures. At the same time, it also reliably reduced pain syndrome developing against the background of bone metastases, which made it possible to classify it as an effective method of symptomatic therapy. The drug received FDA approval back in 2013.
Radium-223 vs Lutetium-177
Both Radium-223 and Lutetium-177 are FDA-approved methods, which are included in the standard guidelines for the treatment of metastatic prostate cancer. However, Radium-223 has a longer half-life as compared to Lutetium-177, which ensures a longer therapeutic effect. In addition to that, Radium-223 acts within a maximum of 10 cells as opposed to Lutetium-177. Such peculiarities help to preserve healthy tissues from being ionized. Nevertheless, some studies indicate increased mortality rates among the patients previously treated with Radium before undergoing Lutetium treatment as compared to Radium-naive individuals. Moreover, disease progression was reported slightly more frequently in Radium-223 treated patients as compared to Lutetium-177. Therefore, in a dispute Radium vs Lutetium, the latter may win based on a number of crucial clinical indicators.
Overall, therapy with Lutetium-177, Actinium-225, and Radium-223 significantly improves the condition of most patients with advanced stages of prostate cancer. This treatment is clearly indicated for men with hormone-resistant prostate cancer with metastases to the bones, lymph nodes, liver, and lungs. The ability to choose between different isotopes allows doctors to personalize the treatment for each patient and achieve excellent therapeutic results.
| Characteristics | Lutetium-177 | Actinium-225 | Radium-223 |
|---|---|---|---|
| Treatment response | 30-80% decrease of tumor volume | 50-80% decrease of number of metastases | 30-50% |
| PSA levels | 70% decrease | 90% decrease of PSA levels | 20-30% decline |
| Disease recurrence rate | decreased in up to 40% | 40-60% decrease of progression* | 15-30% reduction of disease progression |
| Overall survival rates | increased up to 30% | 30% increase* | slightly increases survival |
*Data may vary depending on individual patient factors.
What reactions and side effects can occur?
Today, in the clinical practice of specialized centers and departments of nuclear medicine, only radioactive isotopes with an optimal safety profile and minimal side effects are used. Radionuclide treatment is indicated for debilitated patients with advanced stages of cancer, and therefore doctors pay special attention not only to the effectiveness of the therapy but also to patients' tolerability to it.
The most common side effects of radionuclide therapy include:
- dry mouth – 87% patients;
- nausea – 50% patients;
- fatigue – 50% patients;
- anemia – 13% patients;
- thrombocytopenia – 13% patients;
- lymphocytopenia – 37% patients.
Dry mouth or xerostomia is the most common side effect alongside fatigue. Lutetium-177 and Actinium-225 also have low myelotoxicity, that is, they do not affect the spinal cord when treating metastases in the spine and other bones (the most typical localization of metastases in prostate cancer). Most side effects are temporary and go away on their own within a few days/weeks after the end of the course of treatment. Actinium, Lutetium, and Radium therapy cause significantly less short- and long-term side effects than standard therapies. If necessary, doctors may prescribe symptomatic treatment, such as antiemetic drugs or drugs to improve the patient's general condition.
Success stories from our patients
From Colorado to Berlin: American Patient's Success with Lutetium-177 Treatment
John Baker’s story represents strong determination and persistence in search of the best solution for his problem. John has suffered from prostate cancer for 5 years. When he learned about his diagnosis, John immediately started treatment. He underwent targeted radiotherapy and heat therapy, yet the effect was uninspiring. It was around that time when he found out that cancer spread beyond the prostate. John and his wife faced a significant challenge: wait for the insurance approval, which is typically a time-consuming process, or explore other options. It was exactly when they stumbled upon Booking Health and Lutetium-177.
John and his wife contacted the Booking Health specialists in order to start the treatment as soon as possible. "Everything went like clockwork", says Mr. Baker, recalling his experience of undergoing Lutetium-177 treatment in Germany. Each step of the process was well-planned and clearly communicated. "I never had to worry about where I was going", said John Baker. Treatment itself did not cause any discomfort or side effects. "The only thing that was tiring was the airplane ride", Mr. Baker said laughing. Not only lack of adverse effects as opposed to classical chemotherapy or other protocol methods, but efficacy of Lutetium-177 therapy convinced John the decision to come to Germany for treatment was worthwhile. After one session of treatment, the scan showed that there were no metastatic lesions in the bones. Above that, PSA levels dropped significantly. "I would recommend it to anyone for any cancer problem, not just prostate cancer. It's pretty straightforward, pretty simple", Mr. Baker concluded.
"PSA Dropped to Nothing": US Patient Shares His German Cancer Treatment Journey
New Hope Regained with Actinium-225 PSMA Therapy
Christopher Lambi was fighting prostate cancer for several years. He tried various standard methods including hormones and chemotherapy. However, the disease kept progressing with little hope left when metastases were detected during another planned scanning. Without much enthusiasm, Mr. Lambi decided to look for an alternative opinion abroad. This is how he found out about the Booking Health company.
After a meticulous consultation and comprehensive analysis of the case, Mr. Lambi was recommended to start Actinium-225 PSMA therapy as soon as possible. "I was quite skeptical at first. I knew nothing about this Actinium: what it was and how I will take it". When the patient came, he was picked up from the airport accompanied by a personal translator. "Everything went so smoothly: I had a personal driver, a translator, and a manager, who was literally in contact with me the whole time", said Christopher Lambi. After running medical tests and another in-person consultation, Mr. Lambi started his treatment the very next day. After going through a standard treatment protocol, Christopher Lambi was afraid of severe adverse effects that had a significant impact on his life and work. He was pleasantly surprised to have no side effects after Actinium-225 PSMA therapy. "It was unbelievable – no bleeding, no vomiting, no hair loss. The procedure was easy to go through". Mr. Lambi was even more surprised to see his next scan during the follow-up, which demonstrated that almost 90% of the metastases were gone after just one session. "I was about to lose hope after having so much struggle. Now I can even go back to work. Never dreamt of that again". Christopher Lambi is grateful he once chose to use Booking Health to organize his treatment in Germany. "My best investment so far", said Mr. Lambi with a laugh.
Where to undergo Lutetium-177, Actinium-225, and Radium-223 treatment?
Treatment with radioactive isotopes is offered by the Nuclear Medicine Centers and specialized departments of large university hospitals. Some of the leading medical facilities that a patient from any country in the world can contact are listed below:
- University Hospital Rechts der Isar Munich, Department of Nuclear Medicine. The department is headed by Prof. Dr. med. Wolfgang Weber, whose specialization is radionuclide cancer therapy. The professor has prepared more than 250 articles for leading scientific journals, including the Journal of Clinical Oncology.
- University Hospital of Ludwig Maximilian University of Munich, Department of Nuclear Medicine. The department is headed by Prof. Dr. med. Matthias Brendel. He is a highly qualified expert with extensive experience in nuclear medicine. Prof. Brendel has more than 200 scientific publications and regularly participates in national and international congresses devoted to radioisotope diagnosis and treatment.
- University Hospital Frankfurt am Main, Department of Nuclear Medicine. The head of the department is Prof. Dr. med. Frank Grünwald. The professor has over 30 years of experience in the treatment of patients with radionuclide methods and is one of the best German specialists.
- University Hospital Carl Gustav Carus Dresden, Department of Nuclear Medicine. The head of the department is Prof. Dr. med. Jörg Kotzerke. The professor has been working with methods of radioisotope diagnostics and treatment for more than 30 years and is a board member of the German Society for Nuclear Medicine (DGN).
- University Hospital Erlangen, Department of Nuclear Medicine. The head of the department is Prof. Dr. med. Torsten Kuwert. The professor has been working in nuclear medicine institutes and university clinics for about 30 years, now he specializes in the treatment of prostate cancer and its metastases.
The cost of therapy depends on the level of the country, medical facility, the number of procedures, the need for hospitalization, and other factors.
| Treatment for prostate cancer | Average cost of treatment in Germany | Average cost of treatment in the USA |
|---|---|---|
| Treatment of Prostate Cancer with Metastasis by Lutetium-177-PSMA (LU-177) | €17,000 - €28,000 | starting from $50,000 per cycle |
| Treatment of Prostate Cancer with Metastasis by Actinium-225-PSMA | €18,000 - €29,000 | not widely available |
| Treatment of Prostate Cancer with Bone Metastases by Radium-223 | €12,000 - €15,000 | starting from $32,000 per cycle |
| Lutetium-177-DOTATATE (Lu-177-DOTATATE) therapy for neuroendocrine prostate cancer (NEPC) | €14,000 - €28,000 | not widely available |
Radionuclide treatment in the world's leading hospitals with Booking Health
Nuclear treatment planning, making the radioactive material, and providing high radiation shielding is a technically challenging process. That is why patients often cannot undergo prostate cancer treatment with Lutetium-177, Actinium-225, or Radium-223 in their home country and look for appropriate opportunities in foreign hospitals. Booking Health is a medical tourism agent that has been organizing radionuclide treatment in leading Nuclear Medical Centers for prostate cancer patients from 75 countries for over 12 years.
The Booking Health specialists will help you with the following important factors:
- selection of the most suitable center or department of nuclear medicine and departments of radiology, based on the annual qualification report;
- preliminary preparation of your diagnostic program and treatment for prostate cancer, without unnecessary repetition of previous studies;
- direct communication with your attending physician;
- provision of medical services at their real cost, without overpayments and extra charges for foreign patients (saving up to 50%);
- making an appointment with the doctor for diagnostics and treatment on your required date, allowing you to start treatment without being on a long waiting list;
- independent control of diagnostics and treatment at all stages;
- communication with the hospital after the completion of treatment;
- translation of your medical records and recommendations for further treatment;
- control of the cost of medical services, return of any unspent funds;
- organization of additional diagnostic procedures and courses of therapy, if required;
- top-class service: airline tickets and transfers, organization of accommodation for the patient and the accompanying person;
- interpreting services and support from a personal medical coordinator 24/7.
Leave your request on the Booking Health website and a medical advisor or a patient case manager will contact you shortly. The company's employees will plan your further actions and will accompany you at all stages of your treatment.
Advanced Cancer Treatment: Patient Success Stories with Booking Health
Frequently asked questions of our patients
Contact Medical SpecialistLutetium-177 and Actinium-225 are PSMA-targeted therapies using different types of radiation (beta and alpha, respectively). Radium-223 is more potent for bone metastases. Lutetium-177 has a larger radiation range, while Actinium-225 lasts longer and has a shorter radiation range, which helps to preserve healthy tissues.
These treatments are typically recommended for patients with metastatic castration-resistant prostate cancer (mCRPC), who have not responded well to other treatments like hormone therapy and chemotherapy. The specific choice depends on the quantity and location of metastases, previous treatments, and overall health condition.
Common side effects include fatigue, nausea, and a temporary decrease in blood cell counts. Dry mouth may occur with all PSMA-targeted therapies. Radium-223 may sometimes cause diarrhea. These side effects are generally manageable and less severe than those of traditional chemotherapy.
Clinical trials have shown promising results. For example, Lutetium-177-PSMA therapy has demonstrated PSA response rates of 40-60% and objective response rates of 40-50% in some studies. Actinium-225-PSMA has shown even higher response rates in early trials. Radium-223 has been shown to improve overall survival in patients with bone metastases.
The number of sessions varies by treatment. Lutetium-177-PSMA is typically given in 4-6 sessions, 6-8 weeks apart. Actinium-225-PSMA is often given in 2-4 sessions. Radium-223 is usually administered in 6 injections, 4 weeks apart. Each session involves an intravenous injection of the radioactive drug, followed by a brief period of isolation to manage radiation exposure.
Actinium-225 (Ac-225) is less available than Lutetium-177 (Lu-177) due to a complex manufacturing process. Lu-177 is more widely accessible and already approved for routine clinical use in many countries.
Ac-225 therapy is more expensive than Lu-177 therapy, often costing 2-3 times more per treatment cycle. This difference is due to high production costs of Ac-225.
Preliminary studies suggest that sequential or combination therapy with Ac-225 and Lu-177 may improve efficacy, specifically in patients with resistance to Lu-177. However, more clinical trials are needed to establish safety, optimal sequencing, and long-term outcomes.
Choose treatment abroad and you will for sure get the best results!
See the interview for more information:
RADIONUCLIDE TREATMENT OF PROSTATE CANCER IN GERMANY – interview with Prof. Dr. med. Stefan Dresel
Authors:
The article was edited by medical experts, board certified doctors Dr. Nadezhda Ivanisova and Dr. Vadim Zhiliuk. For the treatment of the conditions referred to in the article, you must consult a doctor; the information in the article is not intended for self-medication!
Our editorial policy, which details our commitment to accuracy and transparency, is available here. Click this link to review our policies.
Sources:
Translational Andrology and Urologye
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