Side effects of Nuclear Medicine Treatment - Overview Lutetium-177, Actinium-225, and Yttrium-90 therapy

Lutetium-177 (Lu-177) Therapy

Lutetium-177 therapy, particularly with Lu-177 dotatate, has emerged as a cornerstone in the treatment of neuroendocrine tumors and metastatic castration-resistant prostate cancer (mCRPC). Clinical trials have demonstrated remarkable efficacy, with up to 65% of neuroendocrine tumor patients experiencing significant tumor shrinkage or stabilization. Additionally, Lu-177 therapy has been shown to extend progression-free survival (PFS) in these patients by an average of 20 to 30 months, offering a crucial improvement in quality of life and longevity.

Despite these positive outcomes, patients undergoing Lu-177 therapy may experience some side effects. The most common of these include fatigue, which can persist for days or weeks following treatment. Nausea is also relatively frequent, though it tends to be mild and manageable with standard antiemetic medications. While vomiting can occur, it is less common and typically short-lived.

Bone marrow suppression is another potential side effect, albeit less common. This can lead to a temporary reduction in blood cell counts, manifesting as anaemia (low red blood cells),  leukopenia  (low white blood cells), or thrombocytopenia (low platelets). These conditions may increase the risk of fatigue, infections, and bleeding, respectively, but they are usually mild and reversible with appropriate monitoring and supportive care.

Renal toxicity  is a less frequent but important consideration, as Lu-177 is partially excreted through the kidneys. To mitigate this risk, patients are closely monitored for kidney function throughout their treatment course. Other less common side effects include  dry mouth  due to salivary gland irradiation,  abdominal discomfort , and  loss of appetite . Rarely, patients with neuroendocrine tumors might experience  hormonal imbalances  due to fluctuations in hormone levels during treatment.

Though exceedingly rare, the risk of  secondary cancers  due to radiation exposure exists, but this is outweighed by the substantial benefits Lu-177 therapy offers in controlling tumor growth and enhancing survival.  Liver toxicity  is another rare side effect, particularly in patients with extensive liver metastases.

Actinium-225 (Ac-225) Therapy

Actinium-225 therapy, especially when used in targeted alpha therapy (TAT), represents a cutting-edge approach in cancer treatment. This therapy has shown exceptional promise in clinical trials, with response rates as high as 70% in patients with metastatic prostate cancer resistant to other treatments. The precise targeting of cancer cells by Ac-225 offers a unique advantage, allowing for potent tumoricidal effects with minimal impact on surrounding healthy tissues.

However, like all therapies, Ac-225 treatment carries the potential for side effects.  Hematological toxicity  is the most common, presenting as  anemia ,  thrombocytopenia , and  leukopenia . These conditions, while concerning, are typically manageable with regular monitoring and may be reversible after therapy completion.

Kidney toxicity  is another key consideration, given that the kidneys play a role in excreting radioactive substances. Close monitoring of renal function is essential, particularly in patients receiving multiple treatment cycles.  Gastrointestinal issues , including  nausea ,  vomiting , and  diarrhea , are also observed but are usually mild and can be controlled with symptomatic treatment.

Fatigue  is a common experience for patients undergoing Ac-225 therapy, often reflecting the body’s response to the potent therapeutic effects.  Mucositis , characterized by inflammation and ulceration of the mucous membranes, particularly in the mouth, can occur, but it is typically short-term and manageable with appropriate care.

Xerostomia , or dry mouth, may result from reduced saliva production, impacting oral health. Some patients may experience  pain at tumor sites , which could indicate the therapy’s effectiveness in shrinking or altering the tumor.  Radiation-induced side effects  are possible but usually localized and mild, such as skin irritation near the treatment area.  Bone marrow suppression  can occur but is generally manageable with routine blood tests and supportive care.

Yttrium-90 (Y-90) PRRT

Yttrium-90 therapy, particularly in the form of Peptide Receptor Radionuclide Therapy (PRRT), is another powerful tool in the treatment of neuroendocrine tumors. Y-90 PRRT has shown to be highly effective, with response rates around 60% in clinical trials. The therapy targets tumor cells with high precision, sparing surrounding healthy tissues and resulting in fewer side effects compared to traditional chemotherapy.

The most commonly reported side effects of Y-90 PRRT include  fatigue  and  nausea , both of which are generally mild and can be easily managed with supportive care.  Abdominal pain  and  diarrhoea  may occur, especially in patients with tumors in the gastrointestinal tract, but these symptoms are usually temporary and manageable.

Blood cell count changes  are a known side effect of Y-90 PRRT, with some patients experiencing  leukopenia ,  thrombocytopenia , or  anaemia . While these changes can increase the risk of infections, bleeding, and fatigue, they are typically mild and reversible with close monitoring.

Less common but more serious side effects include  kidney toxicity  and  hepatotoxicity . As with Lu-177 and Ac-225 therapies, renal function is closely monitored to prevent significant kidney damage.  Bone marrow suppression  is another possible risk, though it is generally well-managed with regular blood tests and supportive treatments.

Radiation-induced organ damage  is a rare but potential risk, particularly in organs adjacent to the treated area. However, the precision of Y-90 PRRT minimizes this risk. Similarly, the risk of  secondary cancers  is extremely low, especially when considering the substantial benefits of tumor control and improved survival rates.

The efficacy of nuclear medicine therapies, including Lu-177, Ac-225, and Y-90, is well-documented, with these treatments offering significant improvements in tumor control, progression-free survival, and overall quality of life for patients with various types of cancer. The precision targeting of these therapies allows for potent anti-tumor effects while minimizing damage to healthy tissues, which is a major advantage over traditional cancer treatments.

While it is important for patients to be aware of the potential side effects associated with these therapies, the risks are generally outweighed by the benefits. Side effects such as fatigue, nausea, and hematological changes are typically mild and manageable with appropriate care. Moreover, with regular monitoring and supportive treatments, more serious side effects like renal toxicity, bone marrow suppression, and organ damage can be effectively mitigated.