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Neuroendocrine Tumors (NETs) are a heterogeneous group of tumors derived from the specialized cells of the neuroendocrine system and can occur in any part of the body.  

NETs are rare tumors that are typically indolent or slow growing in nature. However, therapeutic options are limited in instances of metastatic disease or aggressive transformation, and there is a significant association with morbidity and mortality.   

The median overall survival rate in patients with metastatic liver disease is only 2-4 years.

Lutetium-177 Octreotate Therapy is a form of targeted or “magic bullet” cancer therapy, utilizing Peptide molecules as carrier agents to deliver tumoricidal radioisotopes to the target cancer tissue. This allows the treatment to target and treat the cancerous cells while minimizing damage to healthy, surrounding tissue.

Lutetium-177 Dotatate Therapy relies on the unique nature of Neuroendocrine cancers. These are known to express Somatostatin receptors at a much higher concentration as compared to normal cells.   

Somatostatin is a naturally occurring peptide with various biological functions. It mediates its action through several membrane-bound Somatostatin receptors. Currently, five subtypes of somatostatin receptors have been identified in humans. They are SSRT1, SSRT2, SSRT3, SSRT4, SSRT5. 

The distribution of various SSRT subtypes in human organ systems has been studied fairly extensively and has also been found in many tumors. Neuroendocrine cancers are the archetypical class that have been extensively imaged and treated using Somatostatin analogues. 

However, other tumors such as Neuroblastomas, Meningiomas, Breast Cancers, Lymphomas, Renal Cell Carcinomas, Hepatomas and Pheochromocytomas have been found to express Somatostatin receptors. 

The principle of Somatostatin receptor targeting is based on linking a stable Somatostatin Analogue to a Radioisotope via a chelating agent before administration into the patient, where uptake in the target tissue is dependent on SSRT mediated internalization of the Radioligand. 

Using such radiolabeled Somatostatin Analogues, we can specifically target these cancer cells for imaging and treatment purposes.

Lutetium-177 Dotatate therapy in neuroendocrine cancers has shown good clinical response (approximately 80%), with definite improved survival outcomes and a good safety profile. 

A landmark study compared patients with well-differentiated, metastatic midgut Neuroendocrine tumors who received Lutetium-177 Dotatate therapy or long-term Octreotide injections.  

It was found that Lutetium-177 Dotatate Therapy resulted in markedly longer progression-free survival and a significantly higher response rate than just high dose injected Octreotide. An overall survival benefit was seen at interim analysis.

The major limiting organ system is the kidneys, owing to the Renal Interstitial Irradiation derived from tubular peptide re-absorption and resultant retention in the Interstitium. An estimated median decline in creatinine clearance / renal function is 3.8% per year in patients treated with Lutetium-177 Dotatate.  

To protect the kidneys from such radiation damage, positively charged amino acids have been demonstrated to competitively inhibit the proximal tubular re-absorption of the Radiopeptide (approximate 30-50% reduction of radiation).   

Side effects such as nausea induced by metabolic acidosis secondary to the amino acid do occur in a percentage of patients, but these are usually self-limiting.  The bone marrow is another organ system that can be affected by therapy. Most studies have shown that the marrow effect is generally mild and transient, but patients who have had previous chemotherapy and high radiation doses may develop Myelodysplastic syndromes.  

Lutetium-177 Dotatate therapy can precipitate a hormonal crisis in patients with neuroendocrine cancers, especially in patients with widespread metastasis. However, the risk is low, occurring in approximately 1% of patients.

Patients with Metastatic Neuroendocrine cancers with demonstrable high tracer uptake on Gallium-68 Octreotide scans are the ideal candidates for Lutetium-177 Octreotate Therapy

Absolute Contraindication  

• Pregnancy 
• Severe acute concomitant illness 

Relative Contraindication

• Impaired renal function (GFR < 40 mL/min) 
• Impaired marrow function (platelet < 75 x 109/L, Hb < 90 g/L) 
• Concomitant nephrotoxic drugs
•  Octreotate imaging showing poor tumour tracer avidity

Imaging Studies 

•  DOTATATE imaging study (e.g. Gallium 68 or Copper 64 DOTATATE PET/CT) 

Blood Investigations 

•  Complete Blood Count (CBC) 
• Liver Function Test (LFT) 
• Renal Function Test 
• Cancer Markers (Chromogranin-A)

Functional Status  

• ECOG Status Score

Lu177 Octreotate Therapy can be done on an outpatient basis. It is expected to take approximately 4-6 hours in total, and you will be in the Nuclear Medicine department for the duration of the treatment.   

Intravenous lines will be required for the treatment, and you will be asked to consume fluids to maintain good hydration (approximate 1.0 – 1.5L fluid throughout the day).  

You will be given anti-vomiting medications (e.g. Ondansetron) before the start of the amino acid infusion.   

The amino-acid infusion will begin 30 minutes before administration of Lutetium-177 Octreotate. The amino acid infusion will be given over the next few hours and given concurrently with intravenous fluids. 

Lutetium-177 Octreotate treatment will be given via a slow controlled infusion over 15-20 minutes.  

 After the infusion is done, you are free to walk around the Nuclear Medicine department, but you will be advised to avoid prolonged close contact with other patients.   

You will be observed for potential side effects such as nausea, vomiting, abdominal discomfort or hypotension.  

Once radiation levels are within acceptable limits, you will be free to leave the Nuclear Medicine department.  

If you require admission for observation, we will make the necessary arrangements.  

An appointment for the clinical follow-up will be confirmed or arranged for you prior to discharge.