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 accommo ...

) or ¹⁷⁷Lu DOTA-TATE, trade name Lutathera, is a chelated complex of a

radioisotope A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferr ...

of the element

lutetium Lutetium is a chemical element with the 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

DOTA-TATE DOTA-TATE (DOTATATE, DOTA-octreotate, oxodotreotide, DOTA-(Tyr3)-octreotate, and DOTA-0-Tyr3-Octreotate) is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator. DOTA-TATE can be reacted with the radionuclides ...

, 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 of ...

(PRRT). Specifically, it is used in the treatment of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s which express

somatostatin receptor Somatostatin receptors are receptors for the ligand somatostatin, a small neuropeptide associated with neural signaling, particularly in the post-synaptic response to NMDA receptor co-stimulation/activation. Somatostatin is encoded by a CRE ...

s. Alternatives to ¹⁷⁷Lu-DOTATE include

yttrium-90 Yttrium-90 () is an isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer. Decay undergoes β− decay to zirconium-90 with a half-life of 64.1 hours and a decay energy of 2.28 ...

DOTATATE or

DOTATOC Edotreotide (USAN, also known as (DOTA0- Phe1- Tyr3) octreotide, DOTA-TOC, DOTATOC) is a substance which, when bound to various radionuclides, is used in the treatment and diagnosis of certain types of cancer. When used therapeutically it is an e ...

. 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 during the process of beta decay. There are two forms of beta decay, β� ...

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

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 respon ...

(FDA) considers ¹⁷⁷Lu dotatate to be a first-in-class medication.

Clinical trials and drug approval

The

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

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. 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. 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 is ...

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

(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) based in Rotterdam, Netherlands, affiliated with Erasmus University and home to its faculty of medicine, is the largest and one of the most authoritative scientific University Medical Centers in ...

. 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 ...

designation and

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designation. 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 ...

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 during the process of beta decay. There are two forms of beta decay, β� ...

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

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

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

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

solution (

arginine/lysine Arginine/lysine, sold under the brand name LysaKare, is a fixed-dose combination medication used to protect the kidneys from radiation damage during cancer treatment with a radioactive medicine called lutetium (177Lu) oxodotreotide. Text was ...

) 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.

References

External links

* {{Portal bar , Medicine Chelating agents Lutetium complexes Macrocycles Orphan drugs Radiopharmaceuticals