Fluoroestradiol F-18

Identification

Summary

Fluoroestradiol F-18 is a radiolabeled analog of estradiol used as a contrast agent in the PET imaging of estrogen receptor-positive breast cancer lesions.

Generic Name
Fluoroestradiol F-18
DrugBank Accession Number
DB15690
Background

Fluoroestradiol F-18 is an imaging agent used with positron emission tomography (PET) to detect estrogen receptor-positive breast cancer lesions.4 The ability to image ER-positive tumors in vivo is advantageous in that, while helping to visualize tumor progression/regression, it may also be used to assess for heterogeneity in ER expression across metastases (i.e. to identify sites that no longer express ER) without the need for multiple biopsies.2

Fluoroestradiol F-18 was first granted FDA approval in May 2020, and will be developed by PETNET Solutions, Inc. and Zionexa USA under the brand name Cerianna.5 It is expected to be available in late 2020/early 2021.5

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 289.381
Monoisotopic: 289.170742648
Chemical Formula
C18H23FO2
Synonyms
  • (18F)FES
  • 16-alpha-(18-Fluoro)-17betaestradiol
  • 16-alpha-(18F)Fluoro-17beta-estradiol
  • 16alpha-(18F)Fluoro-17beta-estradiol
  • F-18 16 alpha-Fluoroestradiol
  • F-18 Fes
  • Fes F-18

Pharmacology

Indication

Fluoroestradiol F-18 is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) imaging for the detection of estrogen receptor-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer.4

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Fluoroestradiol F-18 is an analog of estradiol that emits small amounts of radioactivity, allowing it to be detected using PET. Following intravenous administration, it accumulates in cancerous tissues expressing estrogen receptors, thus allowing for visualization of these lesions.4 Fluoroestradiol has a relatively short duration of action - at 2 hours post-injection circulating levels are <5% those at peak concentration.

The uptake of fluoroestradiol F-18 is not specific to breast cancer cells and make occur in any tumor cell expressing estrogen receptors, including those arising from the uterus or ovaries.4

Mechanism of action

Estrogen receptor (ER)-positive breast cancers are a subset of breast cancers in which the cancerous tissue expresses estrogen receptors - these receptors provide a useful target for imaging and treatment agents. Fluoroestradiol F-18 is a fluorinated analog of estradiol that binds to estrogen receptors, allowing for PET imaging of lesions.4

Following exposure in an ER-positive breast cancer cell line (MCF-7), it was found that fluoroestradiol F-18 bound with a Kd of 0.13 ± 0.02 nM, a Bmax of 1901 ± 89 fmol/mg, and a IC50 = 0.085 nM.4

TargetActionsOrganism
UEstrogen receptor alpha
binder
Humans
UEstrogen receptor beta
binder
Humans
Absorption

Not Available

Volume of distribution

As fluoroestradiol and its metabolites undergo enterohepatic circulation,2 it is found primarily distributed within the hepatobiliary system.4 It also distributes to the intestines, heart wall, blood, kidney, uterus, and bladder.4

Protein binding

Following intravenous administration, approximately 95% of fluoroestradiol F-18 is protein-bound4 to both albumin and sex hormone-binding globulin.2

Metabolism

Fluoroestradiol F-18 is highly extracted and metabolized by the liver - at 2 hours post-administration, only 10% of the total activity is attributable to unmetabolized parent drug.2 The majority of generated metabolites are products of glucuronide or sulfate conjugation.3

Route of elimination

Elimination is primarily via urinary and biliary excretion.4 Unbound metabolites comprising mainly glucuronide and sulfate conjugates are secreted in the bile, reabsorbed via enterohepatic circulation, and then renally excreted.2

Half-life

Not Available

Clearance

Fluoroestradiol F-18 is rapidly cleared from the blood by the liver.2

Adverse Effects
Adverseeffects
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Toxicity

Not Available

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
BazedoxifeneBazedoxifene may decrease effectiveness of Fluoroestradiol F-18 as a diagnostic agent.
ClomifeneClomifene may decrease effectiveness of Fluoroestradiol F-18 as a diagnostic agent.
FulvestrantFulvestrant may decrease effectiveness of Fluoroestradiol F-18 as a diagnostic agent.
LasofoxifeneLasofoxifene may decrease effectiveness of Fluoroestradiol F-18 as a diagnostic agent.
OspemifeneOspemifene may decrease effectiveness of Fluoroestradiol F-18 as a diagnostic agent.
RaloxifeneRaloxifene may decrease effectiveness of Fluoroestradiol F-18 as a diagnostic agent.
TamoxifenTamoxifen may decrease effectiveness of Fluoroestradiol F-18 as a diagnostic agent.
ToremifeneToremifene may decrease effectiveness of Fluoroestradiol F-18 as a diagnostic agent.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CeriannaInjection100 mCi/1mLIntravenousZionexa US Corporation2020-05-20Not applicableUS flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
T32277KB09
CAS number
94153-53-4
InChI Key
KDLLNMRYZGUVMA-ZYMZXAKXSA-N
InChI
InChI=1S/C18H23FO2/c1-18-7-6-13-12-5-3-11(20)8-10(12)2-4-14(13)15(18)9-16(19)17(18)21/h3,5,8,13-17,20-21H,2,4,6-7,9H2,1H3/t13-,14-,15+,16-,17+,18+/m1/s1/i19-1
IUPAC Name
(1R,2R,3aS,3bR,9bS,11aS)-2-(¹⁸F)fluoro-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-diol
SMILES
[H][C@@]12C[C@@H]([18F])[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3

References

Synthesis Reference

Kiesewetter DO, Kilbourn MR, Landvatter SW, Heiman DF, Katzenellenbogen JA, Welch MJ: Preparation of four fluorine- 18-labeled estrogens and their selective uptakes in target tissues of immature rats. J Nucl Med. 1984 Nov;25(11):1212-21.

General References
  1. Liu Y, Ma H, Yao J: ERalpha, A Key Target for Cancer Therapy: A Review. Onco Targets Ther. 2020 Mar 11;13:2183-2191. doi: 10.2147/OTT.S236532. eCollection 2020. [Article]
  2. Liao GJ, Clark AS, Schubert EK, Mankoff DA: 18F-Fluoroestradiol PET: Current Status and Potential Future Clinical Applications. J Nucl Med. 2016 Aug;57(8):1269-75. doi: 10.2967/jnumed.116.175596. Epub 2016 Jun 15. [Article]
  3. Mankoff DA, Tewson TJ, Eary JF: Analysis of blood clearance and labeled metabolites for the estrogen receptor tracer [F-18]-16 alpha-fluoroestradiol (FES). Nucl Med Biol. 1997 May;24(4):341-8. doi: 10.1016/s0969-8051(97)00002-4. [Article]
  4. FDA Approved Drug Products: Cerianna (fluoroestradiol F 18) for intravenous injection [Link]
  5. Applied Radiology News Release: PETNET, Zionexa Announce FDA Approval of Cerianna (Fluoroestradiol F 18) [Link]
ChemSpider
9045262
RxNav
2372221
ZINC
ZINC000100657549
Wikipedia
Fluoroestradiol_F-18
FDA label
Download (169 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingDiagnosticBreast Cancer / Ductal Carcinoma in Situ - Category1
2RecruitingDiagnosticEstrogen Receptor Positive / Primary or Recurrent Breast Carcinoma / Stage IV Breast Cancer AJCC v6 and v71
2RecruitingDiagnosticHER2/Neu Negative / Progesterone Receptor Negative / Progesterone Receptor Positive / Stage IV Breast Cancer AJCC v6 and v71
1, 2Enrolling by InvitationDiagnosticEndometriosis1
0TerminatedDiagnosticDeep Fibromatosis/Desmoid Tumor / Familial Adenomatous Polyposis (FAP)1
Not AvailableTerminatedDiagnosticEstrogen Receptor Positive / Recurrent Breast Carcinoma / Stage IV Breast Cancer AJCC v6 and v71

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous100 mCi/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0345 mg/mLALOGPS
logP3.33ALOGPS
logP3.56ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)10.33ChemAxon
pKa (Strongest Basic)-3.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.57 m3·mol-1ChemAxon
Polarizability32.11 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
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
Unknown
Actions
Binder
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. FDA Approved Drug Products: Cerianna (fluoroestradiol F 18) for intravenous injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. FDA Approved Drug Products: Cerianna (fluoroestradiol F 18) for intravenous injection [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Liao GJ, Clark AS, Schubert EK, Mankoff DA: 18F-Fluoroestradiol PET: Current Status and Potential Future Clinical Applications. J Nucl Med. 2016 Aug;57(8):1269-75. doi: 10.2967/jnumed.116.175596. Epub 2016 Jun 15. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Liao GJ, Clark AS, Schubert EK, Mankoff DA: 18F-Fluoroestradiol PET: Current Status and Potential Future Clinical Applications. J Nucl Med. 2016 Aug;57(8):1269-75. doi: 10.2967/jnumed.116.175596. Epub 2016 Jun 15. [Article]

Drug created on May 29, 2020 13:45 / Updated on October 06, 2020 17:43