Lutetium (177Lu) oxodotreotide

Names
Trade names| Lutathera
Other names| Lutetium (177Lu) dotatate

IUPAC name

* (177Lu)lutetium(3+) 2-[4-({[(1R)-1-{[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-4-{[(1S,2R)-1-carboxy-2-hydroxypropyl]-C-hydroxycarbonimidoyl}-6,9,12,15,18-pentahydroxy-7-[(1R)-1-hydroxyethyl]-13-[(1H-indol-3-yl)methyl]-16-[(4-oxidophenyl)methyl]-1,2-dithia-5,8,11,14,17-pentaazacycloicosa-5,8,11,14,17-pentaen-19-yl]-C-hydroxycarbonimidoyl}-2-phenylethyl]-C-hydroxycarbonimidoyl}methyl)-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate

Clinical data
Drug class| Antineoplastic agent
Main uses| Gastroenteropancreatic neuroendocrine tumors (GEP-NET) which express somatostatin receptors[1]
Side effects| Low lymphocytes, liver inflammation, high blood sugar, low potassium, nausea[2]
Routes of
use| Intravenous
External links
AHFS/Drugs.com| Monograph
Legal
License data|

* EU EMA: by INN
* US DailyMed: Lutathera
* US FDA: Lutathera

Legal status|

* UK: POM (Prescription only) [3]
* US: ℞-only [2]
* EU: Rx-only [4]
* In general: ℞ (Prescription only)

Chemical and physical data
Formula| C65H87LuN14O19S2
Molar mass| 1607.58 g·mol−1
3D model (JSmol)|

* Interactive image

SMILES

* CC(C1C(=O)NC(CSSCC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N1)CCCCN)CC2=CNC3=CC=CC=C32)CC4=CC=C(C=C4)O)NC(=O)C(CC5=CC=CC=C5)NC(=O)CN6CCN(CCN(CCN(CC6)CC(=O)[O-])CC(=O)[O-])CC(=O)[O-])C(=O)NC(C(C)O)C(=O)O)O.[Lu+3]

InChI

* InChI=1S/C65H90N14O19S2.Lu/c1-38(80)56-64(96)73-51(63(95)75-57(39(2)81)65(97)98)37-100-99-36-50(72-59(91)47(28-40-10-4-3-5-11-40)68-52(83)32-76-20-22-77(33-53(84)85)24-26-79(35-55(88)89)27-25-78(23-21-76)34-54(86)87)62(94)70-48(29-41-15-17-43(82)18-16-41)60(92)71-49(30-42-31-67-45-13-7-6-12-44(42)45)61(93)69-46(58(90)74-56)14-8-9-19-66;/h3-7,10-13,15-18,31,38-39,46-51,56-57,67,80-82H,8-9,14,19-30,32-37,66H2,1-2H3,(H,68,83)(H,69,93)(H,70,94)(H,71,92)(H,72,91)(H,73,96)(H,74,90)(H,75,95)(H,84,85)(H,86,87)(H,88,89)(H,97,98);/q;+3/p-3/t38-,39-,46+,47-,48+,49-,50+,51+,56+,57+;/m1./s1/i;1+2

* Key:MXDPZUIOZWKRAA-PRDSJKGBSA-K

Lutetium (177Lu) oxodotreotide, sold under the brand name Lutathera, is a medication used to treat gastroenteropancreatic neuroendocrine tumors (GEP-NET) which express somatostatin receptors.[1] It improved time with stable disease from 9 months to 28 months.[5] It is given by injection into a vein.[1]

Common side effects include low lymphocytes, liver inflammation, high blood sugar, low potassium, and nausea.[2] Other side effects may include low platelets, low red blood cells, and tiredness.[5] It works by attaching to somatostatin receptors after which the radioactivity gives the cell.[5]

Lutetium (177Lu) oxodotreotide was approved for medical use in Europe in 2017 and the United States in 2018.[5][1] In the United States it costs about 54,000 USD per dose as of 2021.[6]

## Contents

* 1 Medical uses
* 2 Side effects
* 3 History
* 4 References
* 5 External links

## Medical uses[edit | edit source]

Alternatives to 177Lu-DOTATE include yttrium-90 DOTATATE or DOTATOC. The longer range of the beta particles emitted by 90Y, which deliver the therapeutic effect, may make it more suitable for large tumors with 177Lu reserved for smaller volumes.[7][8]

## Side effects[edit | edit source]

The therapeutic effect of 177Lu derives from the ionizing beta radiation it emits, however this can also be harmful to healthy tissue and organs. The kidneys are particularly at risk as they help to remove 177Lu DOTA-TATE from the body.[9] To protect them, an amino acid solution (arginine/lysine) is administered by slow infusion, starting before the radioactive administration and normally continuing for several hours afterwards.[8][10][11]

## History[edit | edit source]

The European Commission approved lutetium (177Lu) oxodotreotide (trade name Lutathera) "for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults" in September 2017.[12][4]

177Lu DOTA-TATE was approved in the United States for the treatment of SSTR positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults, in January 2018.[2][13][14] This was the first time a radiopharmaceutical had been approved for the treatment of GEP-NETs in the United States.[13]

The U.S. Food and Drug Administration (FDA) approved 177Lu dotatate based primarily on evidence from one clinical trial, NETTER-1 of 229 participants with somatostatin-receptor positive midgut GEP-NETs.[15] Enrolled participants had tumors which could not be surgically removed and were worsening while receiving treatment with octreotide.[15]

Participants were randomly assigned to receive either 177Lu dotatate with long-acting octreotide or long-acting octreotide, at a higher dose, alone.[15] 177Lu dotatate was injected through the vein and long-acting octreotide was injected in the muscle.[15] Both, participants and health care providers knew which treatment was given.[15] The benefit of 177Lu dotatate was evaluated by measuring the length of time that tumors did not grow after treatment and compared it to the control group (progression free survival).[15]

The FDA considered additional data from a second study based on data from 1,214 participants with somatostatin receptor-positive tumors, including GEP-NETS, who received 177Lu dotatate at a single site in the Netherlands, Erasmus MC.[13][15] All participants received 177Lu dotatate with octreotide.[15] Participants and health care providers knew which treatment was given.[15] The benefit of 177Lu dotatate was evaluated by measuring if and how much the tumor size changed during treatment (the overall response rate).[15] Complete or partial tumor shrinkage was reported in 16 percent of a subset of 360 participants with GEP-NETs who were evaluated for response by the FDA.[13] Participants initially enrolled in the study received 177Lu dotatate as part of an expanded access program.[13]

The FDA granted the application for 177Lu dotatate priority review designation and orphan drug designation.[13] The FDA granted the approval of Lutathera to Advanced Accelerator Applications.[13]

The U.S. Food and Drug Administration (FDA) considers 177Lu dotatate to be a first-in-class medication.[16]

## References[edit | edit source]

1. ↑ 1.0 1.1 1.2 1.3 "Lutetium Lu 177 Dotatate Monograph for Professionals". Drugs.com. Archived from the original on 19 October 2021. Retrieved 24 November 2021.
2. ↑ 2.0 2.1 2.2 2.3 "Lutathera- lutetium lu 177 dotatate injection". DailyMed. 4 May 2020. Archived from the original on 16 November 2020. Retrieved 8 November 2020.
3. ↑ "Lutathera 370 MBq/mL solution for infusion - Summary of Product Characteristics (SmPC)". (emc). Archived from the original on 9 July 2021. Retrieved 9 July 2021.
4. ↑ 4.0 4.1 "Lutathera EPAR". European Medicines Agency (EMA). Archived from the original on 11 December 2019. Retrieved 11 December 2019.
5. ↑ 5.0 5.1 5.2 5.3 "Lutathera". Archived from the original on 11 December 2019. Retrieved 24 November 2021.
6. ↑ "Lutathera Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 24 January 2021. Retrieved 24 November 2021.
7. ↑ Ramage JK, Ahmed A, Ardill J, Bax N, Breen DJ, Caplin ME, et al. (January 2012). "Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)". Gut. 61 (1): 6–32. doi:10.1136/gutjnl-2011-300831. PMC 3280861. PMID 22052063.
8. ↑ 8.0 8.1 Bodei L, Mueller-Brand J, Baum RP, Pavel ME, Hörsch D, O'Dorisio MS, et al. (May 2013). "The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours". European Journal of Nuclear Medicine and Molecular Imaging. 40 (5): 800–16. doi:10.1007/s00259-012-2330-6. PMC 3622744. PMID 23389427.
9. ↑ Thompson, Lisa (7 February 2019). "Significance of Amino Acid Solution With Lutetium Lu 177 Dotatate". Oncology Nurse Advisor. Archived from the original on 17 October 2021. Retrieved 12 October 2021.
10. ↑ "LysaKare EPAR". European Medicines Agency (EMA). Archived from the original on 23 July 2020. Retrieved 22 July 2020.
11. ↑ Volterrani D, Erba PA, Carrió I, Strauss HW, Mariani G (10 August 2019). Nuclear Medicine Textbook: Methodology and Clinical Applications. Springer. p. 782\. ISBN 978-3-319-95564-3. Archived from the original on 17 October 2021. Retrieved 12 October 2021.
12. ↑ "European approval of lutetium oxodotreotide for gastroenteropancreatic neuroendocrine (GEP-NET) tumours". ecancer.org. 2017-10-03. Archived from the original on 2018-04-03. Retrieved 2018-04-02.
13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 "FDA approves new treatment for certain digestive tract cancers". U.S. Food and Drug Administration (FDA) (Press release). 26 January 2018. Archived from the original on 11 December 2019. Retrieved 11 December 2019. This article incorporates text from this source, which is in the public domain.
14. ↑ "FDA approves lutetium Lu 177 dotatate for treatment of GEP-NETS". U.S. Food and Drug Administration (FDA) (Press release). 26 January 2018. Archived from the original on 11 December 2019. Retrieved 11 December 2019. This article incorporates text from this source, which is in the public domain.
15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 15.6 15.7 15.8 15.9 "Drug Trials Snapshots: Lutathera". U.S. Food and Drug Administration (FDA). 20 February 2018. Archived from the original on 11 December 2019. Retrieved 11 December 2019. This article incorporates text from this source, which is in the public domain.
16. ↑ New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Archived from the original on 17 September 2020. Retrieved 16 September 2020.

## External links[edit | edit source]

* "Lutetium Lu 177 dotatate". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 2021-10-17. Retrieved 2021-10-12.

Identifiers:|

* ATC code:

* V10XX04 (WHO)

* CAS Number: 437608-50-9
* PubChem CID: 71587735
* DrugBank:

* DB13985

* UNII:

* AE221IM3BB
* acetate: 99R86Y6V0M Y

* KEGG:

* D11033

|

* v
* t
* e

Therapeutic radiopharmaceuticals (V10)

Pain palliation|

* 153Sm
* Lexidronam
* 89Sr (Strontium chloride)

Adrenergic tumors|

* 131I
* Iobenguane

CD20 antibodies|

* 90Y
* Ibritumomab tiuxetan
* 131I
* Tositumomab

Radionuclides|

| alpha emitters|

* 223Ra (Radium chloride)
* 225Ac
* 213Bi

|

beta emitters|

* 32P
* 89Sr
* 90Y
* 131I
* 153Sm
* 165Dy
* 169Er
* 177Lu (Oxodotreotide)
* 186Re
* 198Au

Isotopes used:

* actinium-225
* bismuth-213
* dysprosium-165
* erbium-169
* gold-198
* iodine-131
* lutetium-177
* phosphorus-32
* radium-223
* rhenium-186
* samarium-153
* strontium-89
* yttrium-90

See also: Diagnostic radiopharmaceuticals (V09)
*[EU]: European Union
*[US]: United States
*[UK]: United Kingdom
*[CID]: Compound ID
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template