Lutetium (¹⁷⁷Lu) oxodotreotide (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

) or ¹⁷⁷Lu dotatate, brand name Lutathera, is a chelated complex of a

radioisotope A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess numbers of either neutrons or protons, giving it excess nuclear energy, and making it unstable. This excess energy can be used in one of three ...

of the

element Element or elements may refer to: Science * Chemical element, a pure substance of one type of atom * Heating element, a device that generates heat by electrical resistance * Orbital elements, parameters required to identify a specific orbit of o ...

lutetium Lutetium is a chemical element; it has symbol Lu and atomic number 71. It is a silvery white metal, which resists corrosion in dry air, but not in moist air. Lutetium is the last element in the lanthanide series, and it is traditionally counted am ...

with dotatate, used in

peptide receptor radionuclide therapy Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs). Mechanism A key advantage ...

. Specifically, it is used in the treatment of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s which express somatostatin receptors. It is a radiolabeled somatostatin analog. Alternatives to ¹⁷⁷Lu-dotatate include

yttrium-90 Yttrium-90 () is a radioactive isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the ...

dotatate or

DOTATOC Edotreotide (United States Adopted Name, USAN, also known as (DOTA (chelator), DOTA0-Phenylalanine, Phe1-Tyrosine, Tyr3) octreotide, DOTA-TOC, DOTATOC) is a substance which, when bound to various radionuclides, is used in the treatment and diagnos ...

. The longer range of the

beta particle A beta particle, also called beta ray or beta radiation (symbol β), is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus, known as beta decay. There are two forms of beta decay, β− decay and � ...

s emitted by ⁹⁰Y, which deliver the therapeutic effect, may make it more suitable for large tumors with ¹⁷⁷Lu reserved for smaller volumes The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) considers ¹⁷⁷Lu dotatate to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

Medical uses

In the US, ¹⁷⁷Lu dotatate is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. In the EU, lutetium (¹⁷⁷Lu) oxodotreotide is indicated for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults.

Adverse effects

The therapeutic effect of ¹⁷⁷Lu derives from the ionizing

beta radiation A beta particle, also called beta ray or beta radiation (symbol β), is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus, known as beta decay. There are two forms of beta decay, β− decay and � ...

it emits, however this can also be harmful to healthy tissue and organs. The

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s are particularly at risk as they help to remove ¹⁷⁷Lu dotatate from the body. To protect them, an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

solution ( arginine/lysine) is administered by slow

infusion Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping). An inf ...

, starting before the radioactive administration and normally continuing for several hours afterwards.

History

The

European Commission The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...

approved lutetium (¹⁷⁷Lu) oxodotreotide (brand 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. ¹⁷⁷Lu dotatate 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. This was the first time a

radiopharmaceutical Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...

had been approved for the treatment of GEP-NETs in the United States. The US

(FDA) approved ¹⁷⁷Lu dotatate based primarily on evidence from one clinical trial, NETTER-1 of 229 participants with somatostatin-receptor positive midgut GEP-NETs. Enrolled participants had tumors which could not be surgically removed and were worsening while receiving treatment with octreotide. Participants were randomly assigned to receive either ¹⁷⁷Lu dotatate with long-acting octreotide or long-acting octreotide, at a higher dose, alone. ¹⁷⁷Lu dotatate was injected through the vein and long-acting octreotide was injected in the muscle. Both, participants and health care providers knew which treatment was given. 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). 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 Erasmus University Medical Center (Erasmus MC or EMC) is a teaching hospital based in Rotterdam, Netherlands, affiliated with Erasmus University and home to its faculty of medicine. It is the largest and one of the most authoritative scientific uni ...

. All participants received ¹⁷⁷Lu dotatate with octreotide. Participants and health care providers knew which treatment was given. The benefit of ¹⁷⁷Lu dotatate was evaluated by measuring if and how much the tumor size changed during treatment (the overall response rate). 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. Participants initially enrolled in the study received ¹⁷⁷Lu dotatate as part of an expanded access program. The FDA granted the application for ¹⁷⁷Lu dotatate

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

and

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designations. The FDA granted the approval of Lutathera to

Advanced Accelerator Applications Advanced Accelerator Applications (AAA or Adacap) is a France-based pharmaceutical group, specialized in the field of nuclear medicine. The group operates in all three segments of nuclear medicine (PET, SPECT and therapy) to diagnose and treat ser ...

. In April 2024, the FDA approved ¹⁷⁷Lu dotatate for the treatment of children aged 12 years and older with somatostatin receptor-positive (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors. It was approved for adults in 2018. This is the first FDA approval of a radioactive drug, or radiopharmaceutical, for children aged twelve years of age and older with SSTR-positive gastroenteropancreatic neuroendocrine tumors. Approval for children aged 12 years and older was based on pharmacokinetic, dosimetry, and safety data from NETTER-P (NCT04711135), an ongoing, international, multi-center, open-label, single-arm study of lutetium Lu 177 dotatate in adolescents with locally advanced/inoperable or metastatic SSTR-positive gastroenteropancreatic neuroendocrine tumors or pheochromocytoma/paraganglioma. Approval was also based on the extrapolation of efficacy outcomes observed in NETTER-1 (NCT01578239), a randomized, multicenter, open-label, active-controlled trial in 229 participants with locally advanced/inoperable or metastatic SSTR-positive midgut carcinoid tumors, which supported the original approval of lutetium Lu 177 dotatate in adults. Safety was evaluated in nine pediatric participants in NETTER-P, including four participants with gastroenteropancreatic neuroendocrine tumors. The major outcome measures were absorbed radiation doses in target organs and incidence of adverse reactions after the first treatment cycle. Additional outcome measures included short-term adverse reactions following treatment with lutetium Lu 177 dotatate. The adverse reaction profile observed in NETTER-P was similar to that observed in adults.

References

{{Authority control Chelating agents Lutetium complexes Macrocycles Orphan drugs Radiopharmaceuticals