page_title: Peptide receptor radionuclide therapy
section_title: Mechanism
hierarchical_section_title: Peptide receptor radionuclide therapy / Mechanism
caption_attribution_description: English: The natural somatostatin receptor ligand, the 14 amino acid peptide somatostatin (A), was abridged to the biologically more stable 8 amino acid peptide Octreotide (OC, B), which is used for the treatment of symptomatic neuroendocrine tumors. Introduction of a tyrosine into the 3rd position of the Octreotide sequence resulted in Tyr3-Octreotide (TOC, C), which allows for iodination of the tyrosine residue with the γ-emitter 123I and subsequent somatostatin receptor targeted imaging. For the use in somatostatin receptor targeted radiotherapy TOC was coupled with the chelator DOTA, which led to the study drug, the octapeptide DOTA-TOC (D).
context_page_description: Peptide receptor radionuclide therapy is a type of unsealed source radiotherapy, using a radiopharmaceutical which targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours.
context_section_description: 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. ¹¹¹It 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 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).
caption: 90Y is bound with DOTATOC for PRRT treatments. The natural somatostatin receptor ligand, the 14 amino acid peptide somatostatin (A), was abridged to the biologically more stable 8 amino acid peptide Octreotide (OC, B). Introduction of a tyrosine into the 3rd position of the Octreotide sequence resulted in Tyr3-Octreotide (TOC, C), which allows for iodination of the tyrosine residue with the γ-emitter 123I and subsequent somatostatin receptor targeted imaging. For the use in PRRT TOC was coupled with the chelator DOTA, to form the octapeptide DOTA-TOC (D).
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