Peptide receptor radionuclide therapy

[4] The current generation of PRRT targets somatostatin receptors, with a range of analogue materials such as octreotide and other DOTA compounds.

[5] 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.

[7] Other chelators known as NOTA (triazacyclononane triacetic acid) and HYNIC (hydrazinonicotinamide) have also been experimented with, albeit more for imaging applications.

[17] 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.

[18] 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.

Renal protection is therefore used in some cases, taking the form of alternative substances that reduce the uptake of the kidneys.

[25] 177Lu-DOTATATE (international nonproprietary name: lutetium (177Lu) oxodotreotide) was approved by the FDA in early 2018, for treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

[29][30] In guidance published in August 2018, lutetium (177Lu) oxodotreotide was recommended by NICE for treating unresectable or metastatic neuroendocrine tumours.

[31] The first therapies in Turkey using 177Lu-DOTATATE PRRT were carried out in early 2014, for treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) at the Istanbul University-Cerrahpaşa.

[34][35] Shortly after this, 177Lu-DOTATATE PRRT was provided to Western Australian NET patients on a routine basis under the SAS, as well as under various on-going research trials.

[45] Arginine/lysine can be used to reduce renal radiation exposure during peptide receptor radionuclide therapy with lutetium (177Lu) oxodotreotide.

90 Y 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 123 I 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).