NAV

Flotufolastat F-18

Identification

Summary

Flotufolastat F-18 is a radiopharmaceutical diagnostic agent used in PET imaging to visualize PSMA-positive lesions in men with prostate cancer with suspected metastasis or recurrence.

Brand Names
Posluma
Generic Name
Flotufolastat F-18
DrugBank Accession Number
DB17851
Background

Flotufolastat F-18 (18F-rhPSMA-7.3) is an 18F-labeled ligand that targets the prostate-specific membrane antigen (PSMA).1,3 In patients with recurrent prostate cancer that require localized treatment, the use of 18F-labeled ligands for positron emission tomography (PET) offers accurate diagnostic imaging. Unlike 68Ga-labeled PSMA-targeting ligands, 18F-labeled compounds targeting this protein have a longer half-life and can be produced in larger batches. Flotufolastat F-18 is a diastereoisomer of 18F-rhPSMA-7, and compared to the other diastereoisomers of this compound, flotufolastat F-18 has a faster clearance from blood pool, liver, and kidney, and a high level of accumulation in tumors.1

In May 2023, the FDA approved the use of flotufolastat F-18 for PET of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.3,4 This is the first FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid (rh) technology.4 Additional studies have shown that in patients with primary prostate cancer, the use of flotufolastat F-18 shows led to low interreader variation and a good distinction between primary-tumor activity and bladder background activity.2

Type
Small Molecule
Groups
Approved, Investigational
Structure
Similar Structures
Weight
Average: 1470.63
Monoisotopic: 1469.662295938
Chemical Formula
C63H99FN12O25Si
Synonyms
  • 18F-rhPSMA-7.3
  • Flotufolastat (18F)
  • Flotufolastat F 18
  • rhPSMA-7.3C
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Flotufolastat F-18 is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.3

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Diagnostic agentProstate cancer••••••••••••••••••••• ••••• •••••••• •••••••• ••••••• •••••• ••••••••• •••••• •••••••••••••••••••
Diagnostic agentProstate cancer••••••••••••••••••••• ••••••••••• •••••••••• ••• ••••••• •••••••••• ••••••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

The relationship between the plasma concentrations of flotufolastat F-18 in patients and image interpretation has not been fully elucidated.3 The use of flotufolastat F-18 contributes to the overall long-term cumulative radiation exposure in patients, and long-term radiation exposure is associated with a higher risk of cancer. In addition, image interpretation errors can occur with flotufolastat F-18.3

Mechanism of action

Flotufolastat F-18 binds to the prostate-specific membrane antigen (PSMA) (IC50 = 4.4 nM) expressed on cells, including prostate cancer cells. The fluorine-18 group in flotufolastat F-18 is a ß+ emitting radionuclide that can be detected using positron emission tomography (PET). Since prostate cancer cells overexpress PSMA and flotufolastat F-18 is internalized by cells, this radioactive agent can be used for the diagnostic imaging of prostate cancer patients.3 Compared to morphologic imaging, such as computerized tomography (CT) scans and magnetic resonance imaging (MRI), the use of PET targeting PSMA is a superior technique for the localization of recurrent disease or primary node (N) staging.1

TargetActionsOrganism
AGlutamate carboxypeptidase 2
binder
Humans
Absorption

After flotufolastat F-18 is administered intravenously, it distributes to the liver, heart blood pool and kidneys, with 15.8%, 7.4% and 3.2% of the administered activity, respectively. Flotufolastat F-18 is cleared from the blood.3

Volume of distribution

Not available.

Protein binding

Not available.

Metabolism

After it is injected, flotufolastat F-18 is not metabolized for up to 50 minutes.3

Route of elimination

Flotufolastat F-18 is eliminated by urinary excretion. In the first 2 hours after flotufolastat F-18 is injected, approximately 7% of the administered activity is excreted in the urine. Approximately 15% is excreted 4.5 hours after flotufolastat F-18 is injected.3

Half-life

Not available.

Clearance

Not available.

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

In case of an overdose of flotufolastat F-18, maintain patients hydrated and promote frequent voiding to reduce the effects of radiation exposure. Diuretics can also be used in case of overdose. The product label also recommends estimating the radiation-effective dose administered to the patient, if possible.3 The carcinogenic or mutagenic potential of flotufolastat F-18 in animals has not been evaluated. However, this compound can potentially be mutagenic due to the F-18 radionuclide. Animal studies evaluating the potential impairment of fertility have not been conducted.3

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
Integrate drug-drug
interactions in your software
ApalutamideApalutamide may decrease effectiveness of Flotufolastat F-18 as a diagnostic agent.
BicalutamideBicalutamide may decrease effectiveness of Flotufolastat F-18 as a diagnostic agent.
ClascoteroneClascoterone may decrease effectiveness of Flotufolastat F-18 as a diagnostic agent.
Cyproterone acetateCyproterone acetate may decrease effectiveness of Flotufolastat F-18 as a diagnostic agent.
DarolutamideDarolutamide may decrease effectiveness of Flotufolastat F-18 as a diagnostic agent.
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Posluma (Blue Earth Diagnostics Ltd.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PoslumaInjection158 mCi/1mLIntravenousBlue Earth Diagnostics2023-05-25Not applicableUS flag

Categories

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

Chemical Identifiers

UNII
811W19E3OL
CAS number
2639294-14-5
InChI Key
QMGJNAVROCDAIW-MQNQVPOESA-N
InChI
InChI=1S/C63H99FN12O25Si/c1-62(2,3)102(64,63(4,5)6)39-14-12-38(13-15-39)54(89)67-34-44(69-49(80)20-18-45(60(99)100)76-32-30-74(36-52(85)86)28-26-73(35-51(83)84)27-29-75(31-33-76)37-53(87)88)55(90)70-41(57(93)94)10-7-8-24-65-46(77)21-22-47(78)66-25-9-11-40(56(91)92)68-48(79)19-16-42(58(95)96)71-61(101)72-43(59(97)98)17-23-50(81)82/h12-15,40-45H,7-11,16-37H2,1-6H3,(H,65,77)(H,66,78)(H,67,89)(H,68,79)(H,69,80)(H,70,90)(H,81,82)(H,83,84)(H,85,86)(H,87,88)(H,91,92)(H,93,94)(H,95,96)(H,97,98)(H,99,100)(H2,71,72,101)/t40-,41-,42+,43+,44-,45+/m1/s1/i64-1
IUPAC Name
(2S)-2-({[(1S)-1-carboxy-3-{[(1R)-1-carboxy-4-(3-{[(5R)-5-carboxy-5-[(2R)-2-[(4S)-4-carboxy-4-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]butanamido]-3-({4-[di-tert-butyl((18F)fluoro)silyl]phenyl}formamido)propanamido]pentyl]carbamoyl}propanamido)butyl]carbamoyl}propyl]carbamoyl}amino)pentanedioic acid
SMILES
CC(C)(C)[Si]([18F])(C1=CC=C(C=C1)C(=O)NC[C@@H](NC(=O)CC[C@H](N1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1)C(O)=O)C(=O)N[C@H](CCCCNC(=O)CCC(=O)NCCC[C@@H](NC(=O)CC[C@H](NC(=O)N[C@@H](CCC(O)=O)C(O)=O)C(O)=O)C(O)=O)C(O)=O)C(C)(C)C

References

Synthesis Reference

Bejot, R., et al. (2022). Methods of preparation of 18F labelled silyl-fluoride compounds (WO 2023047138 A1). World Intellectual Property Organization. https://patents.google.com/patent/WO2023047138A1/en?oq=WO2023047138A1

General References
  1. Kroenke M, Schweiger L, Horn T, Haller B, Schwamborn K, Wurzer A, Maurer T, Wester HJ, Eiber M, Rauscher I: Validation of (18)F-rhPSMA-7 and (18)F-rhPSMA-7.3 PET Imaging Results with Histopathology from Salvage Surgery in Patients with Biochemical Recurrence of Prostate Cancer. J Nucl Med. 2022 Dec;63(12):1809-1814. doi: 10.2967/jnumed.121.263707. Epub 2022 Apr 7. [Article]
  2. Langbein T, Wang H, Rauscher I, Kroenke M, Knorr K, Wurzer A, Schwamborn K, Maurer T, Horn T, Haller B, Wester HJ, Eiber M: Utility of (18)F-rhPSMA-7.3 PET for Imaging of Primary Prostate Cancer and Preoperative Efficacy in N-Staging of Unfavorable Intermediate- to Very High-Risk Patients Validated by Histopathology. J Nucl Med. 2022 Sep;63(9):1334-1342. doi: 10.2967/jnumed.121.263440. Epub 2022 Jan 6. [Article]
  3. FDA Approved Drug Products: POSLUMA (flotufolastat F-18) injection for intravenous use (May 2023) [Link]
  4. BioSpace: U.S. FDA Approves Blue Earth Diagnostics’ POSLUMA (Flotufolastat F 18) Injection, First Radiohybrid PSMA-targeted PET Imaging Agent for Prostate Cancer [Link]
RxNav
2637946

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
1RecruitingDiagnosticAdenocarcinoma of Prostate / Biochemically Recurrent Prostate Carcinoma / Localized Prostate Carcinoma1
0Not Yet RecruitingDiagnosticProstate Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous158 mCi/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US11413360No2018-11-222038-11-22US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP-4.1Chemaxon
Physiological Charge-9Chemaxon
Hydrogen Acceptor Count29Chemaxon
Hydrogen Donor Count17Chemaxon
Polar Surface Area564.39 Å2Chemaxon
Rotatable Bond Count45Chemaxon
Refractivity349.66 m3·mol-1Chemaxon
Polarizability148.48 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. Glutamate carboxypeptidase 2
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. Kroenke M, Schweiger L, Horn T, Haller B, Schwamborn K, Wurzer A, Maurer T, Wester HJ, Eiber M, Rauscher I: Validation of (18)F-rhPSMA-7 and (18)F-rhPSMA-7.3 PET Imaging Results with Histopathology from Salvage Surgery in Patients with Biochemical Recurrence of Prostate Cancer. J Nucl Med. 2022 Dec;63(12):1809-1814. doi: 10.2967/jnumed.121.263707. Epub 2022 Apr 7. [Article]
  2. Langbein T, Wang H, Rauscher I, Kroenke M, Knorr K, Wurzer A, Schwamborn K, Maurer T, Horn T, Haller B, Wester HJ, Eiber M: Utility of (18)F-rhPSMA-7.3 PET for Imaging of Primary Prostate Cancer and Preoperative Efficacy in N-Staging of Unfavorable Intermediate- to Very High-Risk Patients Validated by Histopathology. J Nucl Med. 2022 Sep;63(9):1334-1342. doi: 10.2967/jnumed.121.263440. Epub 2022 Jan 6. [Article]
  3. FDA Approved Drug Products: POSLUMA (flotufolastat F-18) injection for intravenous use (May 2023) [Link]

Drug created at May 31, 2023 23:16 / Updated at June 21, 2023 07:11