Identification
- Summary
Lutetium Lu-177 vipivotide tetraxetan is a radioligand therapeutic agent used to treat prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in adults.
- Brand Names
- Pluvicto
- Generic Name
- Lutetium Lu-177 vipivotide tetraxetan
- DrugBank Accession Number
- DB16778
- Background
Lutetium Lu-177 vipivotide tetraxetan is a radioligand therapeutic agent. It consists of a radionuclide, lutetium Lu-177, linked to a moiety that binds to PSMA, a transmembrane protein that is expressed in prostate cancer.3
Lutetium Lu-177 vipivotide tetraxetan was first approved by the FDA on March 23, 2022 as a treatment for prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer.4 In October 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended lutetium Lu-177 vipivotide tetraxetan be granted marketing authorization for the treatment of prostate cancer.6 In December 2022, lutetium Lu-177 vipivotide tetraxetan was approved by the EMA.6,7
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Lutetium Lu-177 vipivotide tetraxetan (DB16778)
- Weight
- Average: 1216.074
Monoisotopic: 1215.422157133 - Chemical Formula
- C49H68LuN9O16
- Synonyms
- 177Lu-PSMA-617
Pharmacology
- Indication
Lutetium Lu 177 vipivotide tetraxetan is a radioligand therapeutic agent indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.3
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic castration-resistant prostate cancer (mcrpc) •••••••••••• ••••• •••••••• •••••••• ••••••••••••••••• •••••••• ••••••••••••••••• •••••••• ••••••• •••••••• ••••••• •••••••• •••••••••••• •••••••••••• Adjunct therapy in treatment of Progressive metastatic castration-resistant prostate cancer (mcrpc) •••••••••••• ••••• •••••••• •••••••• ••••••••••••••••• •••••••• •••••••• •••••••••••• ••••••••••••• ••••••••••••••••• •••••••• ••••••• •••••••• •••••• ••••••••• - Contraindications & Blackbox Warnings
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Lutetium Lu 177 vipivotide tetraxetan is a radioligand that exerts cytotoxic effects on cancer cells.3 Tumor uptake value is 11.2%ID/g.2
In clinical trials of patients with metastatic castration-resistant prostate cancer, treatment with lutetium Lu 177 vipivotide tetraxetan was associated with an 80.4% decline of serum PSA levels and median progression-free survival of 13.7 months. 2
- Mechanism of action
Prostate‐specific membrane antigen (PSMA) is a transmembrane glycoprotein involved in various cellular functions, such as cellular uptake of folate, cell migration, and cell survival. Due to its overexpression on the surface of prostate cancer cells, PMSA remains a useful protein target for targeted diagnostic processes and radionuclide therapy in prostate cancer.1
Lutetium Lu 177 vipivotide tetraxetan consists of lutetium Lu-177, a radionuclide and an active moiety of the drug, linked to a moiety that binds to PSMA. Once administered, lutetium Lu 177 vipivotide tetraxetan binds to PSMA-expressing cells. The beta-minus emission from lutetium Lu-177 delivers radiation to PSMA-expressing cells, as well as to surrounding cells, and induces DNA damage which can lead to cell death.3
Target Actions Organism AProstate-specific antigen binderHumans - Absorption
The blood area under the curve (AUC) (geometric mean coefficient of variation or %CV) of lutetium Lu 177 vipivotide tetraxetan is 52.3 ng x h/mL (31.4%) and the maximum blood concentration (%CV) is 6.58 ng/mL (43.5%) at the recommended dosage.3
- Volume of distribution
The mean volume of distribution (%CV) is 123 L (78.1%). Within 2.5 hours of administration, lutetium Lu 177 vipivotide tetraxetan distributes to gastrointestinal tract, liver, lungs, kidneys, heart wall, bone marrow, and salivary glands.3
- Protein binding
Vipivotide tetraxetan and non-radioactive lutetium vipivotide tetraxetan are 60% to 70% bound to human plasma proteins.3
- Metabolism
Once dissociated from the parent compound, lutetium-177 decays to a stable hafnium-177.3
- Route of elimination
Lutetium Lu 177 vipivotide tetraxetan is primarily eliminated renally.3 It is renally-excreted in the first 48 h following injection.1
- Half-life
The terminal elimination half-life (%CV) of lutetium Lu 177 vipivotide tetraxetan is 41.6 hours (68.8%)3
- Clearance
The mean clearance (CL) (%CV) is 2.04 L/h (31.5%).3
- Adverse Effects
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The LD50 of lutetium Lu 177 vipivotide tetraxetan is unknown. The oral and intraperitoneal LD50 lutetium Lu-177 chloride in mice was 315 mg/kg and 7100 mg/kg, respectively.5
There is limited clinical experience of overdose from lutetium Lu 177 vipivotide tetraxetan. In the event of administration of a radiation overdosage with lutetium Lu 177 vipivotide tetraxetan, reduce the radiation absorbed dose to the patient by increasing the elimination of the radionuclide from the body by frequent micturition or by forced diuresis and frequent bladder voiding. Estimate the effective radiation dose that was applied and treat with additional supportive care measures as clinically indicated.3
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
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Name Kind UNII CAS InChI Key Lutetium Lu-177 complex BRH40Y9V1Q 14265-75-9 OHSVLFRHMCKCQY-NJFSPNSNSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image 1 Pluvicto Injection, solution 1000 MBq/mL Intravenous Novartis Europharm Limited 2023-02-10 Not applicable EU 
Pluvicto Injection, solution 27 mCi/1mL Intravenous Advanced Accelerator Applications Usa, Inc 2022-03-23 Not applicable US 
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- G6UF363ECX
- CAS number
- 1703749-62-5
- InChI Key
- RSTDSVVLNYFDHY-BGOLSCJMSA-K
- InChI
- InChI=1S/C49H71N9O16.Lu/c59-40(28-55-17-19-56(29-42(62)63)21-23-58(31-44(66)67)24-22-57(20-18-55)30-43(64)65)51-27-32-8-12-35(13-9-32)45(68)52-39(26-33-10-11-34-5-1-2-6-36(34)25-33)46(69)50-16-4-3-7-37(47(70)71)53-49(74)54-38(48(72)73)14-15-41(60)61;/h1-2,5-6,10-11,25,32,35,37-39H,3-4,7-9,12-24,26-31H2,(H,50,69)(H,51,59)(H,52,68)(H,60,61)(H,62,63)(H,64,65)(H,66,67)(H,70,71)(H,72,73)(H2,53,54,74);/q;+3/p-3/t32-,35-,37-,38-,39-;/m0./s1/i;1+2
- IUPAC Name
- (177Lu)lutetium(3+) 2-[4,7-bis(carboxylatomethyl)-10-[({[(1r,4r)-4-{[(1S)-1-{[(5S)-5-carboxy-5-({[(1S)-1,3-dicarboxypropyl]carbamoyl}amino)pentyl]carbamoyl}-2-(naphthalen-2-yl)ethyl]carbamoyl}cyclohexyl]methyl}carbamoyl)methyl]-1,4,7,10-tetraazacyclododecan-1-yl]acetate
- SMILES
- [177Lu+3].OC(=O)CC[C@H](NC(=O)N[C@@H](CCCCNC(=O)[C@H](CC1=CC2=CC=CC=C2C=C1)NC(=O)[C@H]1CC[C@H](CNC(=O)CN2CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC2)CC1)C(O)=O)C(O)=O
References
- General References
- Emmett L, Willowson K, Violet J, Shin J, Blanksby A, Lee J: Lutetium (177) PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 2017 Mar;64(1):52-60. doi: 10.1002/jmrs.227. [Article]
- Tateishi U: Prostate-specific membrane antigen (PSMA)-ligand positron emission tomography and radioligand therapy (RLT) of prostate cancer. Jpn J Clin Oncol. 2020 Apr 7;50(4):349-356. doi: 10.1093/jjco/hyaa004. [Article]
- FDA Approved Drug Products: PLUVICTO (lutetium Lu 177 vipivotide tetraxetan) injection, for intravenous use [Link]
- Novartis News: Novartis Pluvicto™ approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer [Link]
- EMA Assessment Report: EndolucinBeta, INN-Lutetium (177 Lu) chloride [Link]
- EMA Summary of Opinion: Pluvicto (lutetium Lu 177 vipivotide tetraxetan) [Link]
- EMA Summary of Product Characteristics: Pluvicto (lutetium 177Lu vipivotide tetraxetan) solution for injection/infusion for intravenous use (December 2022) [Link]
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Other Prostate Cancer 1 3 Active Not Recruiting Treatment Neoplasms of the Prostate 2 3 Completed Treatment Prostate Cancer 1 2 Active Not Recruiting Treatment Genital Neoplasms, Male / Genitourinary tract neoplasm / Neoplasm / Neoplasms by Site / Neoplasms of the Prostate / Prostate Cancer / Prostatic Diseases 1 2 Active Not Recruiting Treatment Metastatic Hormone Naive Prostate Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous 1000 MBq/mL Injection, solution Intravenous 27 mCi/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US10406240 No 2019-09-10 2028-08-15 US US10398791 No 2019-09-03 2034-10-17 US US11318121 No 2008-08-15 2028-08-15 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.064 mg/mL ALOGPS logP 1.52 ALOGPS logP -3.5 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 0.45 Chemaxon pKa (Strongest Basic) 7.01 Chemaxon Physiological Charge -5 Chemaxon Hydrogen Acceptor Count 20 Chemaxon Hydrogen Donor Count 8 Chemaxon Polar Surface Area 373.68 Å2 Chemaxon Rotatable Bond Count 27 Chemaxon Refractivity 294.99 m3·mol-1 Chemaxon Polarizability 107.26 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.
- Specific Function
- Endopeptidase activity
- Gene Name
- KLK3
- Uniprot ID
- P07288
- Uniprot Name
- Prostate-specific antigen
- Molecular Weight
- 28741.1 Da
References
- FDA Approved Drug Products: PLUVICTO (lutetium Lu 177 vipivotide tetraxetan) injection, for intravenous use [Link]
Drug created at March 24, 2022 15:52 / Updated at March 16, 2023 13:01