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Radionuclide Therapies

About

Nuclear medicine therapy uses radiopharmaceuticals targeting specific tumours, such as thyroid, lymphomas or bone metastases, delivering radiation to tumorous lesions as part of a therapeutic strategy to cure, mitigate or control the disease. It can be used either on selective targets or throughout the entire body.

Targeting the tumour

The advancements in medical technology have led to a dramatic surge in the development and availability of new cancer treatments. The treatment of cancer involves different strategies, such as chemotherapy, surgery, radiation therapy and, most recently, targeted therapies, such as the use of radionuclide-based therapies employed in nuclear medicine. External radiotherapy with ionizing radiation is the most frequently employed radiation treatment of cancer patients. In this approach, the primary tumour and a limited area around it is treated through irradiation with high-energy X-rays.

Another treatment option available for certain types of cancer is the use of targeted radionuclide therapy, which is based on administering radioactive substances to patients. Just like chemotherapy, this therapy is a systemic treatment, reaching cells throughout the body by travelling through the bloodstream. However, unlike chemotherapy, these radioactive substances specifically target diseased cells, thus reducing potential side effects.

Radiopharmaceuticals

The radiopharmaceuticals suited for therapeutic purposes are those that strongly bind with the tumour – also known as vehicles with a high tumour affinity. They can transport targeted doses of radiation directly to the tumours and its metastases, thereby sparing normal healthy tissue. The choice of the molecule that carries the radiation to the tumour is determined by its affinity – or binding power – to the tumour’s target structures, such as antigens or receptors. The ionizing radiation emitted by radionuclides linked to the carrier kill cancer cells by damaging their DNA, causing the tumours to shrink.

Purpose

An ideal radiopharmaceutical for therapeutic purposes should:

  • Act exclusively in the cells of malignant tumours
  • Reach all the cells of malignant tumours wherever they are localized
  • Leave healthy tissues and organs unhurt while bringing maximum doses of radiation to the tumour
  • Eliminate malignant tumour cells with great effectiveness.

Types of Therapies

What is Lutetium Octreotate Therapy?
Lutetium-177 Octreotate Therapy is used as a treatment for people with tumours that emerge from the endocrine or nervous system; these are called neuroendocrine tumours (NETs) or carcinoids. This therapy aims to reduce the size of the tumour/s and stop them from multiplying, as well as to ease the symptoms that people may get with these tumours. In a number of patients this can lead to long term remission of the disease.

How Does Lutetium Octreotate Therapy Work?
The body has many different types of receptors, and these help in the communication of signals between the body and the environment. The nervous system is responsible for transmitting these signals, and the endocrine system’s job is to produce the hormones in the body. Somatostatin is the name of a hormone which helps to transmit signals in the body, and controls the production of many other hormones. If a tumour is present in the neuroendocrine system, the tumour cells often express a large number of somatostatin receptors.

Octreotate is chemically similar to somatostatin; however it does not occur naturally in the body. Once it is in the body, it works in a similar way to somatostatin and travels to the neuroendocrine tumour cells. In Lutetium-177 Octreotate Therapy, the octreotate is bound with an isotope called Lutetium-177, which emits beta radiation. It is this radiation that destroys the cancer cells. The octreotate acts as a means of transporting the radiation to the tumour site, so that the whole body does not get exposed to the radiation. This is often referred to as Peptide Receptor Radionuclide Therapy (PRRT).

Is this Treatment Safe?
The radiation used in this therapy is designed to damage and kill the cancer cells. As most of the octreotate travels to the tumour locations, it targets the unhealthy cells in the neuroendocrine system, and any damage to healthy tissue is kept to a minimum. The radiation may, however, impact the kidneys and bone marrow, affecting the production of red blood cells. Blood results are monitored regularly to keep track of any changes in the blood chemistry. If deemed necessary by the physician, amino acids may be given during the treatment, to minimise the effects on the kidneys.

Possible side effects of this therapy may include fatigue, nausea, and a temporary increase in the common symptoms caused by the tumour. Some people may also experience slight hair loss, however this is not permanent. Despite these concerns, we now have over a decade of experience administering Lutetium-177 Octreotate Therapy. Compared to other forms of cancer treatments, patients on PRRT experience minimal and less severe long term side effects.

When Would I Consider Using this Treatment?
Lutetium-177 Octreotate Therapy is primarily used to treat people with NETs when other types of treatment, such as surgery or chemotherapy, are not suitable or are ineffective. This may be due to the size, location and number of tumours present. Lutetium-177 Octreotate is a very specific therapy that can only be used when tumours express a large number of somatostatin receptors. Most NETs show an increase in somatostatin receptors. Other tumours such as head and neck cancers, non-small cell lung cancer, small cell lung cancer and Merkel cell cancer may also express somatostatin receptors. If this therapy is being considered, a diagnostic scan is performed (Gallium Octreotate PET CT) to distinguish if the tumours are positive for somatostatin receptors.

What is Lutetium PSMA Therapy?
Lutetium-177 PSMA Therapy, or Prostate-Specific Membrane Antigen Therapy, is treatment that is increasingly being used for people with advanced prostate cancer. This therapy aims to reduce the size of the tumour/s and stop them from multiplying, as well as to ease the symptoms that people may get with these tumours. It is most often used when the disease has metastasised and when other therapies are poorly tolerated or have failed. In certain patients, it appears to be able to produce long term remission.

How Does Lutetium PSMA Therapy Work?
PSMA is a type of protein located on the surface of a cell and is naturally found on the prostate gland. In someone with prostate cancer, an increased amount of PSMA cell surface receptor is present. If the prostate cancer has spread to other parts of the body (i.e. metastasised) the PSMA will also appear in those areas. Lutetium-177 PSMA Therapy uses a molecule which attaches itself to the PSMA receptors on the cancer cells. Before it is administered, the PSMA molecule is bound with Lutetium-177, which emits beta radiation, a destructive type of radiation that damages the cancer cells when it is in close proximity to them. Over time, it destroys the prostate cancer cells. The PSMA molecule acts as a means of transporting the radiation to the tumour site, so that the whole body does not get exposed to the radiation. This is often referred to as Peptide Receptor Radionuclide Therapy (PRRT).

Is this Treatment Safe?
The radiation used in this therapy is designed to damage and kill the cancer cells. As the PSMA travels to the tumour locations, it targets the unhealthy cells. Aside from the prostate gland and cancer cells, PSMA is also found in the salivary glands, lacrimal glands, kidneys and small intestine, so the PSMA molecule can also take the damaging radiation to these healthy areas. Any damage to these areas, however, is minimal. Side effects of this type of therapy may include a dry mouth, tiredness and a brief decline in the production of blood cells. Blood tests are performed intermittently to ensure the radiation is not damaging healthy tissue.

When Would I Consider Using this Treatment?
This type of therapy is very specific, and is used on people with cancer originating in the prostate. It is used for managing metastatic prostate cancer or prostate cancer that is no longer responsive to other types of treatment. Nearly all types of prostate cancer will produce excessive PSMA, however prior to starting the therapy, a diagnostic scan is performed (Ga-68 PSMA PET CT) to ensure the radiation will target the right areas during treatment.

What is Iodine-131 Therapy?
Iodine-131 therapy uses radiation to damage thyroid tissue, to treat thyroid cancer or a hyperactive thyroid (thyrotoxicosis). The level of this treatment depends on the thyroid problem present. For the treatment of thyroid cancer, the radiation is used to get rid of any excess thyroid tissue after a thyroidectomy. It can also be used to destroy cancer cells that have metastisised from the thyroid gland to other parts of the body, such as the lymph nodes in the neck. If the thyroid is overactive, the radiation reduces the activity of the thyroid to achieve a normal state.

How Does Iodine-131 Therapy Work?
Iodine is required by the thyroid gland in order to produce the thyroid hormones. Iodine-131 is a radioactive form of Iodine, emitting beta radiation that destroys cancer cells. Usually given as a capsule, the Iodine-131 gets taken up by thyroid cells, the only cells in the body that can absorb Iodine. The radiation emitted damages any cancer cells that may be present, or reduces the overall activity of the thyroid to a normal level.

Is this Treatment Safe?
Iodine-131 therapy has been used for over 70 years and is considered to be a safe treatment. Above certain dosage levels, precautions may need to be taken when around children and the general public. As a cancer therapy treatment, an inpatient hospital stay is required to prevent the radiation exposure to others. This treatment is not to be used while pregnant, as the radiation has the potential to adversely affect the unborn child. Side effects after undergoing this treatment are uncommon but may include a tender throat for several days and very occasionally nausea. Further side effects seen in high-dose thyroid cancer treatments include altered taste and an occasional dry mouth. In very rare cases, side effects of multiple high-dose treatments may include the development of secondary cancers in the bone marrow, kidney, bowel and bladder many years after treatment. These side effects are more common in patients that require multiple high-dose treatments, although this is now uncommon in modern thyroid cancer practice.

When Would I Consider Using this Treatment?
This therapy is one of the most common treatments for the thyroid conditions such as thyroid cancer and thyrotoxicosis. Early stage cancer of the thyroid is usually treated with solely surgery (thyroidectomy). Iodine-131 Therapy is considered for patients with large tumours, used after a thyroidectomy to destroy any remaining cancerous thyroid tissue in the thyroid gland area, or to destroy any tumours that may have spread elsewhere in the body.

What is Radium-223 Therapy?
Radium-223 Therapy is a type of treatment that is used for people who have prostate cancer that has spread, or metastasised, to the bones. Its aim is to damage the cancer cells in the bone, leading to the tumours shrinking in size, or even disappearing altogether. It is also used to reduce or diminish pain that can be associated with cancer in the bones.

How Does Radium-223 Therapy Work?
Radium-223 is a radioactive form of the element radium, and releases a type of radiation called alpha radiation. This type of radiation can be quite destructive, however it can only travel very short distances. Radium-223 shares similar chemical properties to calcium, and acts in a similar way in the body. Cancer cells in the bone take up more calcium than usual. As Radium-223 acts in a similar way to calcium, it travels directly to the tumours location and emits radiation that destroys the unhealthy cells. This makes Radium-223 Therapy a very effective treatment for bone cancers, as any damage to healthy cells is kept to a minimum.

Is This Treatment Safe?
The radiation used in Radium-223 therapy has a very high energy level, which makes it very destructive. However, due to the nature of this radiation, it only travels very short distances (two to ten cells in depth), ensuring that the damage occurs to the cancer cells in the bone and not to healthy cells. This minimal uptake into healthy cells means that the side effects associated with this therapy are negligible. This may include a temporary reduction in the number of blood cells produced, and infrequently, symptoms of nausea, vomiting and diarrhoea.

When Would I Consider Using this Treatment?
This treatment is a very specific type of therapy so it can only be used for people who have had prostate cancer that has spread to the bones. As this is such a new therapy, there is limited research involving other types of cancer, for example breast cancer. It is currently only approved for use in patients with prostate cancer, though may be of benefit to other patients with bone metastases. This therapy may ease the pain that often comes with cancer in the bones. If this therapy is being considered, a diagnostic scan is performed (Technetium-99m bone scan) to ensure the radiation will target the right areas during treatment. Radium-223 Therapy is now covered by Department of Veterans’ Affairs (DVA).

What is Yttrium-90 Radiosynovectomy Therapy?
Yttrium-90 Radiosynovectomy Therapy is a treatment for painful joints caused by arthritis or other types of joint diseases. It aims to destroy specific tissue that causes redness and swelling, often alleviating severe pain experienced by sufferers of joint disease.

How Does Yttrium-90 Radiosynovectomy Therapy Work?
Inflammation is a protective response that increases blood and fluids in a particular area causing redness and swelling in tissues and joints. The pain associated with inflammation is primarily due to a large amount of fluid build up in a small area. The fluid that lubricates the joints and allows them to move freely is produced by the synovial membrane. Synovitis is the inflammation of the synovial membrane, and is a symptom of certain types of arthritis or joint diseases. Severe pain associated with synovitis can be treated with Yttrium-90 Radiosynovectomy Therapy. This treatment utilizes Yttrium-90, an isotope emitting beta radiation, to destroy painful tissue and stop fluid secretion, reducing joint inflammation. Yttrium-90 is injected into the joint cavity, and the radiation emitted destroys the diseased area over one month. The synovium is eventually replaced by the body and the new synovium is disease and pain free.

Is this Treatment Safe?
The radiation used in Yttrium-90 Radiosynovectomy therapy has a very high energy level, which makes it very destructive. Due to the nature of this radiation, it only travels very short distances, ensuring that damage to healthy tissue is kept to a minimum. Yttrium-90 Radiosynovectomy Therapy is effective in destroying unhealthy tissue; however, patients may experience minor side effects. A rare potential side effect is radiation dermatitis, a skin reaction to the radiation used. Another extremely rare complication is septic arthritis, where the joint becomes infected. These side effects are minimized by using particular injection techniques.

When Would I Consider Using this Treatment?
Yttrium-90 Radiosynovectomy Therapy is used on patients experiencing severe joint pain due to arthritis, or other types of joint disease. It is often used as an alternative to surgery, where the synovium removed. Surgery can be expensive, result in long recovery time and has a higher possibility of complications. Yttrium-90 Radiosynovectomy Therapy is an alternative for patients with medical conditions, such as heart problems, that deem them unsuitable for surgery.

Primary tumors often metastasize when tumor cells migrate via the blood supply or lymphatics to seed other sites for tumor progression. Particularly in prostate, breast, and lung cancer, metastases to the skeleton are often encountered in later stages of the disease process. Although bone metastases are often encountered in end-stage disease, multi-year survival is not uncommon, and palliation of the pain usually associated with the skeletal metastases can greatly improve quality of life and movement. A variety of palliative strategies are available, and depending on the anatomical location and number of metastases and other personalized factors, the use of therapeutic radioisotopes is particularly appealing since these agents for treatment of multi-foci are easy to administer, often on an outpatient basis, and provide palliation which last several months and can be repeated. This chapter discusses the development and use of radio-labeled palliative agents used in nuclear medicine practice

How the therapy works

The biological action of a radiopharmaceutical is determined by the form of ionizing radiation emitted by the radionuclide. While imaging procedures in nuclear medicine require radionuclides that will emit γ (gamma) radiation able to penetrate the body, a different class of radionuclides possessing optimal relative biological effectiveness is needed for radionuclide therapy. The radionuclides best suited for tumour therapy are those emitting ionizing radiation with short penetration into the tissue, such as α (alpha) or β (beta) emitters, which release their energy in the proximity of their targets.