Peptide receptor radionuclide therapy

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Peptide receptor radionuclide therapy
CT scan of non-functioning pancreatic NET before and 6 months after successful treatment with four cycles of 177Lu-DOTATATE.
Specialtyoncology

Peptide receptor radionuclide therapy (PRRT) is a type of

neuroendocrine tumours (NETs).[1]

Mechanism

A key advantage of PRRT over other methods of radiotherapy is the ability to target delivery of therapeutic

beta emitters, therapy can be achieved, as in PRRT.[4]

The current generation of PRRT targets

Auger electrons emitted, which can have a therapeutic effect in high doses.[6]

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).

PRRT radiopharmaceuticals are constructed with three components; the radionuclide,

receptor 5 compared to DOTA-octreotide (DOTATOC).[6][10]

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-

bismuth-213 or actinium-225 labelled DOTATOC are of particular interest.[17]

A comparative cohort study of 1051

DOTATOC group (1.4% versus 10.1%, p=0.001).[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

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.[19][20]

Dosimetry

Therapeutic PRRT treatments typically involve several gigabecquerels (GBq) of activity.[21] 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.[22] Radionuclides that can be used for imaging include gallium-68, technetium-99m and fluorine-18.[21]

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.[5][21][23]

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.[24] 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.[25]

United States

177Lu-DOTATATE (international nonproprietary name: lutetium (177Lu) oxodotreotide) was approved by the FDA in early 2018, for treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs).[26][27]

Europe

Marketing authorisation for 177Lu-DOTATATE was granted by the European Medicines Agency on 26 September 2017.[28] 90Y-DOTATOC (international nonproprietary name: yttrium (90Y) edotreotide) and 177Lu-DOTATOC are designated as orphan drugs, but have not yet received marketing authorisation.[29][30]

United Kingdom

In guidance published in August 2018, lutetium (177Lu) oxodotreotide was recommended by NICE for treating unresectable or metastatic neuroendocrine tumours.[31]

Turkey

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.[32]

Australia

Research in Australia into the use of lutetium-177-labelled antibodies for various cancers began in the Department of Nuclear Medicine at Fremantle Hospital and Health Service (FHHS), Fremantle, Australia in the late 1990s.[33] The first therapies in Australia using 177Lu-DOTATATE PRRT for NET began in February 2005 on a trial basis under the Therapeutic Goods Administration's (TGA) Special Access Scheme (SAS) and compassionate usage of unapproved therapeutic goods.[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.[36][37][38][39][40][41][42][43][excessive citations]

In Australia, most centres synthesise the lutetium-177 peptide on-site from lutetium-177 chloride and the appropriate peptide.[44]

Side effects

Like any form of

ionising radiation can harm healthy tissue as well as the intended treatment target. Radiation from lutetium (177Lu) oxodotreotide can cause damage when the medicine passes through tubules in the kidney.[45] Arginine/lysine can be used to reduce renal radiation exposure during peptide receptor radionuclide therapy with lutetium (177Lu) oxodotreotide.[45]

See also

References

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  2. ^ "Fact Sheet: What Is Peptide Receptor Radionuclide Therapy (PRRT)?". SNMMI. Retrieved 12 May 2018.
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  25. ^ "Information about lutetium (177Lu) oxodotreotide". NICE. National Institute for Health and Care Excellence. 29 August 2018. Retrieved 3 September 2018.
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  27. ^ Office of the Commissioner (26 January 2018). "FDA approves new treatment for certain digestive tract cancers". Food and Drug Administration. Retrieved 20 May 2018.
  28. ^ "Lutathera". European Medicines Agency. Retrieved 24 May 2018.
  29. ^ "Yttrium (90Y) edotreotide". European Medicines Agency. Retrieved 24 May 2018.
  30. ^ "EU/03/14/1269". European Medicines Agency. Retrieved 7 November 2020.
  31. ^ "Lutetium (177Lu) oxodotreotide for treating unresectable or metastatic neuroendocrine tumours [TA539]". National Institute for Health and Care Excellence. 29 August 2018. Retrieved 3 September 2018.
  32. ^ Kabasaka, Levent. "Lu-177-PSMA Real World Clinical Study: Out-patient or In-patient Treatment" (PDF). BNMS. Retrieved 2 August 2021.
  33. ^ Turner, J Harvey (1998-12-31). "Radiolanthanides in therapeutic nuclear oncology (Conference) | ETDEWEB". www.osti.gov. Retrieved 2019-10-04.
  34. ^ Australian Government Department of Health Therapeutic Goods Administration (2018-01-05). "Special Access Scheme: Guidance for health practitioners and sponsors". Therapeutic Goods Administration (TGA). Retrieved 2019-10-04.
  35. ^ "COSA:NETs guidelines/Radionuclide Therapy - Clinical Guidelines Wiki". wiki.cancer.org.au. Retrieved 2019-10-04.
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  45. ^ a b "LysaKare EPAR". European Medicines Agency (EMA). Retrieved 22 July 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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