Prostate Cancer and Systemic Radionuclide Therapy (Atom Therapy)

Prostate cancer is the second most common cancer in men in our country, and the most common in some countries. In addition to diagnosing and staging prostate cancer, imaging methods are of great importance in follow-up for recurrent disease. Treatment options are determined after the examinations performed after the diagnosis. Surgery, radiotherapy, hormone-based treatments, and chemotherapy and immunotherapy in advanced stages of the disease are the treatment methods. Radionuclide treatments are resistant to hormone-based treatments; It is used in patients with metastatic prostate cancer that has spread to distant organs such as lymph nodes or bones and lungs.

Systemic radionuclide therapy (known as atom therapy) is a type of targeted (molecular = smart) radiation therapy. Contrary to the known radiotherapy, it can be expressed as the dispersion of radioactive materials given by vascular or oral route to all tumor foci within the body (internal) and simultaneous targeted radiation therapy of all, instead of irradiation applied to a certain area from the external radiation source (external). The radioactive drug targeting cancer cells finds the targeted tumor foci and simultaneously all of them are treated with radiation. Depending on the half-life of the radioactive material used, this radiation therapy takes place inside the patient’s own body for days and weeks. In these targeted therapies, the harmful effects of radiation on non-target tissues and organs are limited. It can be defined as targeted, individualized radiation therapy since certain molecules of the tumor are targeted. In all types of cancer, there is no molecular radionuclide treatment option that does not harm normal tissues and can have a lethal effect on tumor cells. This treatment is possible if there is a target that is intensely present in cancer tissue, absent in normal cells, or very rare, and a molecule capable of combining with a radioactive substance that can reach this target.

Male sex hormones (androgens) in the bloodstream can affect the growth, cell proliferation and spread of prostate cancer. Therefore, treatments to reduce androgen levels are widely used in the treatment of prostate cancer. Prostate cancer that continues to progress despite androgen-suppressing treatments is referred to as ‘castration-resistant prostate cancer’ and there is often bone spread of the disease. Chemotherapy, immunotherapy, radiotherapy, and second generation hormone-based treatments should be started in order to control the disease and alleviate the pain that may occur. In this period, radionuclide treatments, which can be expressed as hormone-resistant metastatic prostate cancer, also took their place among the options.

IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

SYSTEMIC RADYONUCLIDE TREATMENTS

  1. BONE TARGET RADYONUCLIDE THERAPY:

They target new bone tissue that forms in and around bone metastases. If there is no spread to organs or tissues other than bone, the following molecular radionuclide therapies are used to relieve pain and treat castration-resistant prostate cancer that has spread to bone:

  • Lutetium-177 EDTMP

  • Radium-223 dichloride

  • Strontium-89 chloride

  • Samarium-153

  • Others…

Bone-targeted radionuclide therapy is administered intravenously and can be repeated periodically.

  1. PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGET RADIONUCLILD THERAPIES

Prostate-specific membrane antigen protein (PSMA) is a biomarker for prostate cancer. In many types of the disease, cancer cells are found at much higher levels than in normal prostate tissue. Its level in non-prostatic tissues and organs is limited. Because of this unique property in prostate cancer cells, PSMA radionuclide is an ideal target molecule in therapy and imaging. PSMA labeled with radioactive material; In addition to the tumor in the prostate gland, it allows imaging or treatment of all lymph nodes, bones, lung, liver and other distant foci of spread. When PSMA is labeled with radionuclides such as positron emitting Gallium-68 or Fluor-18, tumoral tissues of prostate cancer can be visualized with high sensitivity and specificity with Positron Emission Tomography scanners; When labeled with Lutetium-177, which emits beta rays, or Actinium-225, which emits alpha particles, specific and targeted treatment of all tumoral tissues can be performed with the effect of therapeutic radiation. Molecules that are common targets for therapy and imaging are called ‘theranostics’. Theranostics is an emerging field in the medical world. It is an approach that detects the tumor and its metastases by imaging with a tumor-specific drug, where the drug will reach and to what extent, and can be treated with a specific drug whose effect on the diseased tissue is known beforehand.

Like many medical procedures and drugs, radionuclide treatments also have some side effects. The decision of suitability for treatment is made by PSMA-targeted PET-CT, apart from blood tests.

Most types of prostate cancer have high levels of PSMA at levels required for treatment. Ga-68 PSMA PET/CT performed before Lu-177 PSMA treatment determines whether tumors and their metastases carry PSMA receptors at the desired level. Lu-177 is a radioactive element that emits beta rays with therapeutic effects. When Lu-177 PSMA is administered intravenously, it reaches tumor foci with high levels of PSMA receptor. Lutetium-177, which is attached to the tumor cell through PSMA in this way, destroys the cancer cells with the effect of radiation. Since PSMA is at least 1000 times higher in cancer cells than in normal tissues, other areas of the body are exposed to much less radiation.

Lutetium-177 PSMA is administered by intravenous infusion in about half an hour. Although it varies according to the centers, it may require 1 night in a special isolation room. In the first 12 hours after the treatment, a large amount of radioactivity is excreted through the urine, and the part that is retained in the tumor foci initiates its therapeutic effect. Treatment is applied for 2-6 cycles at intervals of 6-8 weeks.

Possible side effects; It is a temporary decrease in blood cell production as a result of nausea, dry mouth, fatigue, weakness, decreased appetite, decreased kidney function, and suppression of bone marrow, especially in patients with extensive bone lesions. Appropriate patient selection and appropriate treatment dose planning are very important for the development of side effects.

Actinium-225 PSMA Treatment; In terms of its mechanism of action, Lutetium-177 is the same as PSMA treatment. In this PSMA-targeted treatment, Actinium-225, which emits alpha rays, is used differently. While short-range but high-energy alpha rays cause cell death by creating double-stranded DNA breaks in tumor cells with a very high therapeutic effect in the area where they are kept, they do not harm the healthy tissues in their close neighborhood.

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