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Lutetium (177Lu) chloride

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Lutetium (177Lu) chloride.png
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Lutetium (177Lu) chloride

塩化ルテチウム (177Lu)

FormulaLu. 3Cl
CAS16434-14-3
Mol weight281.326

2022/9/15 EMA 2022, Illuzyce

EndolucinBeta

(177Lu)lutetium(3+) trichloride

Diagnostic aid, Radioactive agent

Lutetium 177 is an isotope of a rare-earth lanthanide metal lutetium. Radioactive decay of Lu 177 produces electrons with low energies making the isotope suitable for treatment of metastatic disease. A complex of Lu177 and somatostatin analog DOTA-TATE was approved by the FDA for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, including foregut, midgut, and hindgut neuroendocrine tumors in adults. It is marketed under a tradename Lutathera. Lutetium in the complex with other carriers – phosphonates and monoclonal antibodies – was investigated in clinical trials as radiotherapy to prostate, ovarian, renal and other types of cancer.Lutetium (177Lu) chloride is a radioactive compound used for the radiolabeling of pharmaceutical molecules, aimed either as an anti-cancer therapy or for scintigraphy (medical imaging).[5][6] It is an isotopomer of lutetium(III) chloride containing the radioactive isotope 177Lu, which undergoes beta decay with a half-life of 6.65 days.

Medical uses

Lutetium (177Lu) chloride is a radiopharmaceutical precursor and is not intended for direct use in patients.[5] It is used for the radiolabeling of carrier molecules specifically developed for reaching certain target tissues or organs in the body. The molecules labeled in this way are used as cancer therapeutics or for scintigraphy, a form of medical imaging.[5] 177Lu has been used with both small molecule therapeutic agents (such as 177Lu-DOTATATE) and antibodies for targeted cancer therapy[8][9]

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Clinical data
Trade namesLumark, EndolucinBeta, Illuzyce
AHFS/Drugs.comLumark UK Drug Information
EndolucinBeta UK Drug Information
License dataEU EMAby INN
Pregnancy
category
AU: X (High risk)[1][2]
ATC codeNone
Legal status
Legal statusAU: Unscheduled [3][4]EU: Rx-only [5][6][7]In general: ℞ (Prescription only)
Identifiers
showIUPAC name
CAS Number16434-14-3
PubChem CID71587001
DrugBankDBSALT002634
ChemSpider32700269
UNII1U477369SN
KEGGD10828
CompTox Dashboard (EPA)DTXSID20167745 
Chemical and physical data
FormulaCl3Lu
Molar mass281.32 g·mol−1
3D model (JSmol)Interactive image
hideSMILES[Cl-].[Cl-].[Cl-].[177Lu+3]

Contraindications

Medicines radiolabeled with lutetium (177Lu) chloride must not be used in women unless pregnancy has been ruled out.[5]

Adverse effects

The most common side effects are anaemia (low red blood cell counts), thrombocytopenia (low blood platelet counts), leucopenia (low white blood cell counts), lymphopenia (low levels of lymphocytes, a particular type of white blood cell), nausea (feeling sick), vomiting and mild and temporary hair loss.[5]

Society and culture

Legal status

Lutetium (177Lu) chloride (Lumark) was approved for use in the European Union in June 2015.[5] Lutetium (177Lu) chloride (EndolucinBeta) was approved for use in the European Union in July 2016.[6]

On 21 July 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Illuzyce, a radiopharmaceutical precursor.[10] Illuzyce is not intended for direct use in patients and must be used only for the radiolabelling of carrier medicines that have been specifically developed and authorized for radiolabelling with lutetium (177Lu) chloride.[10] The applicant for this medicinal product is Billev Pharma ApS.[10] Illuzyce was approved for medical use in the European Union in September 2022.[7]

References

  1. ^ “Lutetium (177Lu) Chloride”Therapeutic Goods Administration (TGA). 21 January 2022. Archived from the original on 5 February 2022. Retrieved 5 February 2022.
  2. ^ “Updates to the Prescribing Medicines in Pregnancy database”Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
  3. ^ “TGA eBS – Product and Consumer Medicine Information Licence”Archived from the original on 5 February 2022. Retrieved 5 February 2022.
  4. ^ http://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=1C7A40803A3A3F94CA2587D4003CE48A&agid=(PrintDetailsPublic)&actionid=1 Archived 30 July 2022 at the Wayback Machine[bare URL PDF]
  5. Jump up to:a b c d e f g “Lumark EPAR”European Medicines Agency (EMA)Archived from the original on 25 October 2020. Retrieved 7 May 2020. Text was copied from this source under the copyright of the European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. Jump up to:a b c “EndolucinBeta EPAR”European Medicines Agency (EMA)Archived from the original on 28 October 2020. Retrieved 7 May 2020. Text was copied from this source under the copyright of the European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. Jump up to:a b “Illuzyce EPAR”European Medicines Agency (EMA). 18 July 2022. Archived from the original on 22 September 2022. Retrieved 21 September 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  8. ^ Lundsten S, Spiegelberg D, Stenerlöw B, Nestor M (December 2019). “The HSP90 inhibitor onalespib potentiates 177Lu‑DOTATATE therapy in neuroendocrine tumor cells”International Journal of Oncology55 (6): 1287–1295. doi:10.3892/ijo.2019.4888PMC 6831206PMID 31638190.
  9. ^ Michel RB, Andrews PM, Rosario AV, Goldenberg DM, Mattes MJ (April 2005). “177Lu-antibody conjugates for single-cell kill of B-lymphoma cells in vitro and for therapy of micrometastases in vivo”. Nuclear Medicine and Biology32 (3): 269–78. doi:10.1016/j.nucmedbio.2005.01.003PMID 15820762.
  10. Jump up to:a b c “Illuzyce: Pending EC decision”European Medicines Agency. 21 July 2022. Archived from the original on 30 July 2022. Retrieved 30 July 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

External links

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