Peptide receptor radionuclide therapy

Dr Lizette Louw educates on peptide receptor radionuclide therapy, a nuclear medicine therapy, and explains why it’s an effective treatment choice for neuroendocrine tumours.

You can listen to this article below, or by using your favourite podcast player at pod.link/oncologybuddies

What is nuclear medicine?

Nuclear medicine is a specialised area of medical imaging that uses small amounts of radioactivity to examine organ function. The radioactive atom is linked to a specific molecule, depending on which organ system will be imaged. This radioactive molecule, called a radiopharmaceutical or radiotracer, then images a physiological process in the body, without interfering with the physiological process.

Nuclear medicine can be used for therapy as well, specifically for thyroid disease, neuroendocrine cancers and prostate cancer.

What are neuroendocrine tumours?

Neuroendocrine tumours (NETs) originate in cells that produce hormones in response to nervous system signals; endocrine refers to the tumours’ hormone characteristic.

The most common sites of origin are bowel, lung or pancreas. Tumours are categorised as grade 1, 2 or 3 based on tumour cell growth rate, measured on histology samples as the Ki-67 index. The higher the Ki-67 is, the faster the tumour growth, and the more aggressive the tumour.

Tumours that release hormones are termed functional tumours and those that don’t are termed non-functional tumours.

Symptoms

Symptoms are often very vague and non-specific and may continue for several years prior to the final diagnosis. Functional tumours may cause more specific symptoms due to the hormones released.

For example: flushing, high blood pressure, diarrhoea or intermittent sudden drop in blood glucose.

At the time of diagnosis, the tumour has often spread already. However, if it’s still limited, surgery could be curative.

Somatostatin and its receptors

Somatostatin is a normal hormone which interacts with normal body cells via cell surface receptors, causing growth. The majority of NETs have an excess of somatostatin receptors, and thus overreact to normal somatostatin levels, leading to excessive tumour growth. Nuclear medicine makes use of a somatostatin analogue for both imaging and therapy for NETs. This analogue binds to the excess somatostatin receptors, but without eliciting the same cascade reaction inside the cell and therefore doesn’t stimulate tumour growth.

For imaging, either octreotide or DOTA-peptides is used. The latter is used for PET/CT imaging and is more sensitive and specific than either CT or MRI, as PET/CT can detect small tumour lesions missed on CT or MRI. DOTA PET/CT is used for the confirmation of NETs, staging after histology diagnosis, and assessing treatment response. It also guides oncologists and surgeons in therapy choices. Patients with very bright DOTA-peptides uptake in the tumour sites will benefit from either octreotide-type injections or nuclear medicine therapy. If there is very little DOTA-peptides uptake within the tumour, chemotherapy will be more effective.

Octreotide blocks the binding of somatostatin to its receptors and is given as an injection every three to four weeks. If this treatment fails, and surgery or local radiation isn’t an option, nuclear medicine therapy can be considered.

Peptide receptor radionuclide therapy

For this therapy, the same DOTA peptide molecule is used as for PET/CT scan, but it’s linked to a different radioactivity that releases damaging radiation rather than imaging radiation. This therapy is called peptide receptor radionuclide therapy (PRRT).

Treatment is a one-day procedure, takes about four hours, and is repeated every eight to 12 weeks for a total of four cycles, after which the PET/CT is repeated to assess treatment response.

Less than 10% of patients will have no response and further progression. The majority of patients will have a response ranging from minimal to near complete response, but will all have an improved quality of life, reduction of their symptoms and improved overall survival.

PRRT side effects are minimal and include mild to moderate fatigue, some pain or discomfort in the various tumour areas and mild nausea. Patients with functional tumours may experience a hormonal surge during the treatment infusion, but a life-threatening hormone reaction is extremely rare.

Although the cost of around R70 000 per cycle sounds high, the total annual cost would be around half of high-dose octreotide, and only 40% of everolimus’ cost, which has significantly more side effects.

Final thought

Nuclear medicine plays a critical role in accurate imaging of NETs throughout the course of disease. PRRT is an effective treatment choice with minimal side effects.

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