Piflufolastat F 18
Identification
- Summary
Piflufolastat F 18 is a radiopharmaceutical diagnostic agent used with PET to image PSMA-positive lesions for the diagnosis of metastatic or recurrent prostate cancer.
- Brand Names
- Pylarify
- Generic Name
- Piflufolastat F 18
- DrugBank Accession Number
- DB14805
- Background
Prostate cancer is the most common non-cutaneous malignancy affecting men in North America2 - despite this, an ongoing challenge in prostate cancer therapy is the difficulty in imaging the extent and location of tumor metastases and recurrences.4 The images generated by positron emission tomography (PET) are less detailed than those obtained via MRI or CT, but are more sensitive and can reveal cancerous tissue in any area of the body provided the tissue is expressing the appropriate target protein. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in many tissues that plays a role in folate uptake and neurotransmitter release - it is expressed in the prostate at levels roughly 1000-fold greater than elsewhere in the body, and even higher in prostate cancer tissue.1 As such, it has become a desirable target for PET imaging of prostate cancer tissues.
Piflufolastat F18, also called [F-18]-DCFPyL, is a urea-based radiopharmaceutical that binds to PSMA and allows for the visualization of cancerous prostate tissue. It was first approved by the FDA in May 2021 under the brand name Pylarify and aims to allow for earlier and more accurate detection of suspected prostate cancer metastases or recurrences.5 On July 28, 2023, the EMA also approves Piflufolastat F18 under the brand name PYLCLARI for primary staging or localizing recurrence of prostate cancer.7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 441.403
Monoisotopic: 441.152526384 - Chemical Formula
- C18H23FN4O8
- Synonyms
- (18F)DCFPyL
- [F-18]-DCFPyL
- 18F-DCFPyL
- DCFPyL F-18
- Piflufolastat F 18
- Piflufolastat F-18
- PyL
Pharmacology
- Indication
Piflufolastat F18 is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer who have suspected metastases and are candidates for initial definitive therapy and for men with a suspected recurrence of prostate cancer based on elevated prostate-specific antigen (PSA) levels by the FDA.3 It is approved by the EMA for the primary staging of patients with high-risk prostate cancer prior to initial curative therapy and for localizing recurrence of prostate cancer in patients with a suspected recurrence based on increasing serum prostate-specific antigen (PSA) levels after primary treatment with curative intent.6
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Prostate cancer •••••••••••• ••••• ••••••••• •••••••• •••••• ••••••••• Diagnostic agent Prostate cancer •••••••••••• ••••• •••• •••• •••••••• ••••••• ••••••••• ••• •••••••••• ••••••• ••••••••• Diagnostic agent Prostate cancer •••••••••••• ••••••••• ••• •••••••••• •••••••• ••••••••• •••••••••• ••••••••• Diagnostic agent Recurrent prostate cancer •••••••••••• ••••••••• ••••• •••••••• •••••••• ••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Not Available
- Mechanism of action
Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that plays a role in dietary folate uptake and the release of neurotransmitters within the brain. While PSMA is expressed in many tissues, its expression levels in the prostate are roughly 1000-fold greater than elsewhere in the body and even higher in prostate cancer tissue.1
Piflufolastat F18 binds to PSMA and therefore, in combination with PET imaging, allows for the visualization of PSMA-positive lesions associated with prostate cancer.3
Target Actions Organism AGlutamate carboxypeptidase 2 binderHumans - Absorption
Not Available
- Volume of distribution
Piflufolastat F 18 distributes to the kidneys (16.5% of administered activity), liver (9.3%), and lung (2.9%), within 60 minutes of intravenous administration.3
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Piflufolastat F18 is eliminated via urinary excretion - within 8 hours of intravenous administration, approximately 50% of an administered dose is excreted in the urine.3
- Half-life
The half-life of distribution of piflufolastat F18 is 0.17 ± 0.044 hours and its elimination half-life is 3.47 ± 0.49 hours.3
- Clearance
Not Available
- Adverse Effects
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- Toxicity
There are no data regarding the effects of overdosage with piflufolastat F18. In the event of overdose, the amount of absorbed radiation can be mitigated by administered fluids and encouraging frequent bladder voiding. The use of diuretics to encourage voiding may also be considered.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.
Drug Interaction Integrate drug-drug
interactions in your softwareApalutamide Apalutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent. Bicalutamide Bicalutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent. Cyproterone acetate Cyproterone acetate may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent. Darolutamide Darolutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent. Enzalutamide Enzalutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Pylarify (Lantheus Holdings, Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Pylarify Injection 80 mCi/1mL Intravenous Progenics Pharmaceuticals, Inc. 2021-05-26 Not applicable US Pylclari Injection, solution 1500 MBq/mL Intravenous Curium Pet France 2023-08-02 Not applicable EU Pylclari Injection, solution 1000 MBq/mL Intravenous Curium Pet France 2023-08-02 Not applicable EU
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 3934EF02T7
- CAS number
- 1207181-29-0
- InChI Key
- OLWVRJUNLXQDSP-MVBOSPHXSA-N
- InChI
- InChI=1S/C18H23FN4O8/c19-13-6-4-10(9-21-13)15(26)20-8-2-1-3-11(16(27)28)22-18(31)23-12(17(29)30)5-7-14(24)25/h4,6,9,11-12H,1-3,5,7-8H2,(H,20,26)(H,24,25)(H,27,28)(H,29,30)(H2,22,23,31)/t11-,12-/m0/s1/i19-1
- IUPAC Name
- (2S)-2-({[(1S)-1-carboxy-5-{[6-(¹⁸F)fluoropyridin-3-yl]formamido}pentyl]carbamoyl}amino)pentanedioic acid
- SMILES
- OC(=O)CC[C@H](NC(=O)N[C@@H](CCCCNC(=O)C1=CC=C([18F])N=C1)C(O)=O)C(O)=O
References
- Synthesis Reference
Shan L: 2-(3-{1-Carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-p entanedioic acid. [PubMed:23256224]
- General References
- Shan L: 2-(3-{1-Carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-p entanedioic acid . [Article]
- Osborne JR, Akhtar NH, Vallabhajosula S, Anand A, Deh K, Tagawa ST: Prostate-specific membrane antigen-based imaging. Urol Oncol. 2013 Feb;31(2):144-54. doi: 10.1016/j.urolonc.2012.04.016. Epub 2012 May 31. [Article]
- FDA Approved Drug Products: Pylarify (piflufolastat F 18) injection for intravenous use [Link]
- American Cancer Society: Tests to Diagnose and Stage Prostate Cancer [Link]
- OncLive: FDA Approves Piflufolastat F18 PSMA PET Imaging Agent for Prostate Cancer [Link]
- EMA Approved Drug Products: Pylclari (piflufolastat F 18) injection for intravenous use [Link]
- Curium Receives Marketing Authorization in the EU for PYLCLARI(TM), an Innovative 18F-PSMA PET Tracer Indicated in Adults With Prostate Cancer [Link]
- External Links
- Human Metabolome Database
- HMDB0304843
- ChemSpider
- 32702072
- 2556616
- ChEMBL
- CHEMBL4297334
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Not Yet Recruiting Diagnostic Adenocarcinoma of Prostate / Castration Resistant Prostate Cancer / Castration-sensitive Prostate Cancer 1 4 Not Yet Recruiting Diagnostic Metastatic Castration-Resistant Prostate Cancer (mCRPC) / Metastatic Castration-resistant Prostate Carcinoma / Prostate Cancer 1 4 Not Yet Recruiting Treatment Prostate Cancer 1 4 Recruiting Diagnostic Prostate Cancer 1 3 Completed Diagnostic Adenocarcinoma of Prostate / Metastatic Prostate Cancer / Prostate Cancer / Recurrent Prostate Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 80 mCi/1mL Injection, solution Intravenous 1000 MBq/mL Injection, solution Intravenous 1500 MBq/mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8778305 No 2014-07-15 2030-09-21 US US9861713 No 2018-01-09 2029-07-31 US US10947197 No 2021-03-16 2037-06-09 US US8487129 No 2013-07-16 2027-11-07 US US11851407 No 2017-06-09 2037-06-09 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.191 mg/mL ALOGPS logP -0.37 ALOGPS logP -0.32 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 2.99 Chemaxon Physiological Charge -3 Chemaxon Hydrogen Acceptor Count 9 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 195.02 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 101.38 m3·mol-1 Chemaxon Polarizability 42 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0032-0983500000-6a973d2ebf2c76627002 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0903000000-e0cbc1f04fc22d54859b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0fb9-2981100000-b613e1cf07b2a5f3c3cd Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-1912000000-425c6104c9b620a79f86 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0udr-4954000000-88f1bde895cef236269e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0udl-6920000000-a9da383356c6af3b0fdc Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Tetrahydrofolyl-poly(glutamate) polymer binding
- Specific Function
- Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of fola...
- Gene Name
- FOLH1
- Uniprot ID
- Q04609
- Uniprot Name
- Glutamate carboxypeptidase 2
- Molecular Weight
- 84330.015 Da
References
Drug created at May 20, 2019 14:28 / Updated at July 28, 2023 21:40