physics

Peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy is a physics topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Peptide receptor radionuclide therapy rather than just read about it. In short: Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs). Mechanism A key advantage of PRRT over other methods of radiotherapy is the ability to target delivery of therapeutic radionuclides directly to the tumour or target site.

Key takeaways

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Reference excerpt

Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs).

Mechanism A key advantage of PRRT over other methods of radiotherapy is the ability to target delivery of therapeutic radionuclides directly to the tumour or target site. This works because some tumours have an abundance (overexpression) of peptide receptors, compared to normal tissue. A radioactive substance can be combined with a relevant peptide (or its analogue) so that it preferentially binds to the tumour. With a gamma emitter as the radionuclide, the technique can be used for imaging with a gamma camera or PET scanner to locate tumours. When paired with alpha or beta emitters, therapy can be achieved, as in PRRT. The current generation of PRRT targets somatostatin receptors, with a range of analogue materials such as octreotide and other DOTA compounds. These are combined with indium-111, lutetium-177 or yttrium-90 for treatment. 111In is primarily used for imaging alone, however in addition to its gamma emission there are also Auger electrons emitted, which can have a therapeutic effect in high doses.

PRRT radiopharmaceuticals are constructed with three components; the radionuclide, chelator, and somatostatin analogue (peptide). The radionuclide delivers the actual therapeutic effect (or emission, such as photons, for imaging). The chelator is the essential link between the radionuclide and peptide. For 177Lu and 90Y this is typically DOTA (tetracarboxylic acid, and its variants) and DTPA (pentetic acid) for 111In. Other chelators known as NOTA (triazacyclononane triacetic acid) and HYNIC (hydrazinonicotinamide) have also been experimented with, albeit more for imaging applications. The somatostatin analogue affects biodistribution of the radionuclide, and therefore how effectively any treatment effect can be targeted. Changes affect which somatostatin receptor is most strongly targeted. For example, DOTA-lanreotide (DOTALAN) has a lower affinity for receptor 2 and a higher affinity for receptor 5 compared to DOTA-octreotide (DOTATOC).

Applications The body of research on the effectiveness of current PRRT is promising, but limited. Complete or partial treatment response has been seen in 20-30% of patients in trials treated with 177Lu-DOTATATE or 90Y-DOTATOC, among the most widely used PRRT drugs. When it comes to comparing these two PRRT, Y-labeled and Lu-labeled PRRTs, it appears that Y-labeled is more effective for larger tumors, while Lu-labeled is better for smaller and primary tumors. The lack of ɤ-emission with Y-labeled PPRTs is also an important difference between Lu peptides and Y peptide. In particular, with Y-labeled PRRT it becomes difficult to set up a dose of radiations specific to the patient's needs. In most cases PRRT is used for cancers of the gastroenteropancreatic and bronchial tracts, and in some cases phaeochromocytoma, paraganglioma, neuroblastoma or medullary thyroid carcinoma. Various approaches to approve effectiveness and limit side effects are being investigated, including radiosensitising drugs, fractionation regimes and new radionuclides. Alpha emitters, which have much shorter ranges in tissue (limiting the effect on nearby healthy tissue), such as bismuth-213 or actinium-225 labelled DOTATOC are of particular interest. A comparative cohort study of 1051 neuroendocrine tumor patients undergoing 90Y-DOTATOC (n=910) or 177Lu-DOTATOC (n=141) reported no significant difference in overall survival between the groups. However, patients with high tumor accumulation and multiple lesions seemed to benefit from 90Y-DOTATOC, while patients with low tumor burden, solitary lesions and extra-hepatic disease experienced more favorable outcome on 177Lu-DOTATOC. There were significantly fewer cases of transitory hematotoxicity in the 177Lu-DOTATOC group compared with the 90Y-DOTATOC group (1.4% versus 10.1%, p=0.001). The randomized controlled phase III Neuroendocrine Tumors Therapy (NETTER-1) trial evaluated the efficacy and safety of 177Lu-DOTATATE as compared with high-dose octreotide long-acting repeatable (LAR) in patients with advanced progressive somatostatin-receptor positive midgut neuroendocrine tumors. Patients were randomly assigned to receive either 177Lu-DOTATATE and octreotide LAR at a dose of 30 mg every four weeks for symptom control (n=116) or to only receive octreotide LAR at a dose of 60 mg every four weeks (n=113, control group). In total, 200 out of the 231 patients entered long-term follow-up. Final overall survival in the intention-to-treat population was median 48.0 months in the 177Lu-DOTATATE group versus median 36.3 months in the control group (p=0.30). In other words, there was numerical difference of 11.7 months, not reaching statistical significance. 177Lu-DOTATATE was associated with limited acute toxic effects. In neuroendocrine tumor patients with advanced well-differentiated disease and progression on somatostatin analogs, 177Lu-DOTATATE is likely to reduce the risk of disease progression and be associated with quality-of-life benefits.

Dosimetry Therapeutic PRRT treatments typically involve several gigabecquerels (GBq) of activity. Several radiopharmaceuticals allow simultaneous imaging and therapy, enabling precise dosimetric estimates to be made. For example, the bremsstrahlung emission from 90Y and gamma emissions from 177Lu can be detected by a gamma camera. In other cases, imaging can be performed by labelling a suitable radionuclide to the same peptide as used for therapy. Radionuclides that can be used for imaging include gallium-68, technetium-99m and fluorine-18. Currently used peptides can result in high kidney doses, as the radiopharmaceutical is retained for relatively long periods. Renal protection is therefore used in some cases, taking the form of alternative substances that reduce the uptake of the kidneys.

Availability PRRT is not yet widely available, with various radiopharmaceuticals at different stages of clinical trials. The cost of small volume production of the relevant radionuclides is high. The cost of Lutathera, a commercial 177Lu-DOTATATE product, has been quoted by the manufacturer as £71,500 (€80,000 or $94,000 in July 2018) for 4 administrations of 7.4 GBq.

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Illustrations

Worked examples

Example 1 — a first encounter with Peptide receptor radionuclide therapy

Start with the simplest possible case. Write down what Peptide receptor radionuclide therapy claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In physics, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Peptide receptor radionuclide therapy before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Peptide receptor radionuclide therapy ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Peptide receptor radionuclide therapy

In research: Peptide receptor radionuclide therapy appears in physics research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Peptide receptor radionuclide therapy in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Peptide receptor radionuclide therapy is common in secondary-school and first-year university syllabi. It links to neighbouring topics Cancer treatments, Medical physics, Nuclear medicine procedures, so understanding it makes those chapters shorter.
In everyday life: Look for Peptide receptor radionuclide therapy outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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Frequently asked questions

What is Peptide receptor radionuclide therapy in simple terms?

Why does Peptide receptor radionuclide therapy matter?

Because it connects several physics ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Peptide receptor radionuclide therapy?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Peptide receptor radionuclide therapy.