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 20215 under the brand name Pylarify and aims to allow for earlier and more accurate detection of suspected prostate cancer metastases or recurrences.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
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.3

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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

TargetActionsOrganism
AGlutamate carboxypeptidase 2
binder
Humans
Absorption

Not Available

Volume of distribution

Within 60 minutes of intravenous administration, piflufolastat F18 distributes to the kidneys, liver, and lungs.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
Adverseeffects
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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.
DrugInteraction
ApalutamideApalutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent.
BicalutamideBicalutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent.
Cyproterone acetateCyproterone acetate may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent.
DarolutamideDarolutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent.
EnzalutamideEnzalutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent.
FlutamideFlutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent.
NilutamideNilutamide may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent.
RelugolixRelugolix may decrease effectiveness of Piflufolastat F 18 as a diagnostic agent.
Interactions
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Food Interactions
No interactions found.

Products

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International/Other Brands
Pylarify (Lantheus Holdings, Inc.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PylarifyInjection80 mCi/1mLIntravenousProgenics Pharmaceuticals, Inc.2021-05-26Not applicableUS flag

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
  1. Shan L: 2-(3-{1-Carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-p entanedioic acid . [Article]
  2. 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]
  3. FDA Approved Drug Products: Pylarify (piflufolastat F 18) injection for intravenous use [Link]
  4. American Cancer Society: Tests to Diagnose and Stage Prostate Cancer [Link]
  5. OncLive: FDA Approves Piflufolastat F18 PSMA PET Imaging Agent for Prostate Cancer [Link]
ChemSpider
32702072
RxNav
2556616
ChEMBL
CHEMBL4297334

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedDiagnosticAdenocarcinoma, Prostate / Prostate Cancer / Prostate Cancer - Recurrent / Refractory, metastatic hormone-refractory Prostate cancer1
2Active Not RecruitingDiagnosticProstate Cancer1
2CompletedDiagnosticProstate Cancer1
2CompletedDiagnosticRenal Cell Adenocarcinoma1
2Not Yet RecruitingDiagnosticAdenocarcinoma, Prostate / Neoplasms of the Prostate / Prostate Cancer1
2Not Yet RecruitingDiagnosticProstate Cancer1
2RecruitingDiagnosticBreast Cancer / HER 2 Negative Breast Cancer / Metastatic Breast Cancer1
2RecruitingDiagnosticCastrate Sensitive Prostate Cancer1
2RecruitingDiagnosticNeoplasms of the Prostate / Prostate Cancer / Prostatic Neoplasms / Refractory, metastatic hormone-refractory Prostate cancer1
2RecruitingDiagnosticNeoplasms of the Prostate / Prostate Cancer / Refractory, metastatic hormone-refractory Prostate cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous80 mCi/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8778305No2014-07-152030-09-21US flag
US9861713No2018-01-092029-07-31US flag
US10947197No2021-03-162037-06-09US flag
US8487129No2013-07-162027-11-07US flag

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.191 mg/mLALOGPS
logP-0.37ALOGPS
logP-0.32ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)2.99ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area195.02 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity101.38 m3·mol-1ChemAxon
Polarizability42 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets2
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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
  1. Shan L: 2-(3-{1-Carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-p entanedioic acid . [Article]
  2. FDA Approved Drug Products: Pylarify (piflufolastat F 18) injection for intravenous use [Link]

Drug created on May 20, 2019 14:28 / Updated on June 02, 2021 20:04