Lu-PSMA-617, sold under the brand name Pluvicto, is 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 ...

medication used for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

(mCRPC).

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 ...

(¹⁷⁷Lu) vipivotide tetraxetan is a targeted

radioligand A radioligand is a microscopic particle which consists of a Radiopharmaceutical, therapeutic radioactive isotope and the cell-targeting compound - the ligand. The ligand is the target binding site, it may be on the surface of the targeted cancer c ...

therapy. The most common adverse reactions include fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. Lu-PSMA-617 is a radioconjugate composed of PSMA-617, a human prostate-specific membrane antigen (PSMA)-targeting ligand, conjugated to the beta-emitting radioisotope

lutetium-177 Naturally occurring lutetium (71Lu) is composed of one stable isotope 175Lu (97.41% natural abundance) and one long-lived radioisotope, 176Lu with a half-life of 37 billion years (2.59% natural abundance). Forty radioisotopes have been characteriz ...

, with potential antineoplastic activity against PSMA-expressing tumor cells. Upon intravenous administration of Lu-PSMA-617, it targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by ¹⁷⁷Lu through the specific delivery of beta particle radiation. PSMA, a tumor-associated antigen and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells. Lu-PSMA-617 was approved for medical use in the United States in March 2022, and in the European Union in December 2022. 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 it 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

Lu-PSMA-617 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 adults with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. In March 2025, the US

expanded the indication for Lu-PSMA-617 to include adults with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibitor therapy and are considered appropriate to delay taxane-based chemotherapy.

History

In 2006, scientists from

Purdue University Purdue University is a Public university#United States, public Land-grant university, land-grant research university in West Lafayette, Indiana, United States, and the flagship campus of the Purdue University system. The university was founded ...

designed a targeting ligand that bound with high affinity and specificity to PSMA on prostate cancer cells and patented its ability to target attached radionuclides such as ¹⁷⁷Lu, ^99mTc, ⁶⁸Ga, etc. to prostate cancers. The patents were licensed to Endocyte in 2007. In 2012, scientists at

German Cancer Research Center The German Cancer Research Center (known as the Deutsches Krebsforschungszentrum or simply DKFZ in German language, German) is a national cancer research center based in Heidelberg, Germany. It is a member of the Helmholtz Association of German ...

and

University Hospital Heidelberg University Hospital Heidelberg () is a university hospital in Heidelberg, Germany and is with 1,991 beds one of the largest medical centers in the country. It is closely linked to Heidelberg University Medical School (Heidelberg University Fac ...

improved the drug's affinity, patented, and licensed to ABX advanced biomedical compounds, a small German pharmaceutical company, for early clinical development. In 2017, the ABX patent was also acquired by Endocyte and Endocyte together with the above two sets of patents was acquired by

Novartis Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by re ...

in 2018. Efficacy and safety was initially investigated as a compassionate access treatment in Germany with high tumor targeting and low doses to normal organs. Physician-scientists from the Peter MacCallum Cancer Centre conducted a phase 2 trial demonstrating high response rates, low toxicity and reduction in pain in men with metastatic castration-resistant cancer who progressed after conventional treatments. The ANZUP co-operative trials conducted the first randomized, multicentre trial comparing lutetium vipivotide tetraxetan to cabazitaxel chemotherapy. Efficacy was evaluated in VISION, a randomized (2:1), multicenter, open-label trial that evaluated Lu-PSMA-617 plus best standard of care (BSoC) (n=551) or BSoC alone (n=280) in men with progressive, prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer. All participants received a GnRH analog or had prior bilateral orchiectomy. Participants were required to have received at least one androgen receptor pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. Participants received Lu-PSMA-617 7.4 GBq (200 mCi) every 6 weeks for up to a total of 6 doses plus BSoC or BSoC alone. Efficacy was evaluated in PSMAfore (NCT04689828), a randomized, multicenter, open-label trial enrolling 468 participants with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer and progression on one androgen receptor pathway inhibitor, who the investigator considered appropriate for delay of taxane-based chemotherapy. Participants were randomized (1:1) to receive Lu-PSMA-617 (7.4 GBq 00 mCievery six weeks for six doses) or a change in androgen receptor pathway inhibitor. Participants who progressed on the androgen receptor pathway inhibitor arm were allowed to crossover to the experimental therapy. The US

granted the application for Lu-PSMA-617

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

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...

designations.

Society and culture

Regulatory status

In October 2022, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Pluvicto, intended for the treatment of prostate cancer. The applicant for this medicinal product was Novartis Europharm Limited. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Lu-PSMA-617 was approved for medical use in the European Union in December 2022.

References

{{Authority control Lutetium complexes Drugs developed by Novartis Radiopharmaceuticals Vipivotide tetraxetan chelates