Choline C 11

Identification

Name
Choline C 11
Accession Number
DB09277
Type
Small Molecule
Groups
Approved, Investigational
Description

Choline C 11 is a marker for cellular proliferation as its main molecule is a precursor for the biosynthesis of phospholipids which are essential components of all cell membranes.[4] It was developed by MCPRF and FDA first approved in September 2012.

Structure
Thumb
Synonyms
  • 11C-choline
  • 11C-choline chloride
Categories
Not Available
UNII
381E0BTR5Q
CAS number
87591-54-6
Weight
Average: 138.62
Monoisotopic: 138.0878256
Chemical Formula
C5H14ClNO
InChI Key
SGMZJAMFUVOLNK-ULWFUOSBSA-M
InChI
InChI=1S/C5H14NO.ClH/c1-6(2,3)4-5-7;/h7H,4-5H2,1-3H3;1H/q+1;/p-1/i1-1;
IUPAC Name
(2-hydroxyethyl)((¹¹C)methyl)dimethylazanium chloride
SMILES
[Cl-].C[N+](C)([11CH3])CCO

Pharmacology

Indication

Choline C11 is indicated for its use in positron emission tomography (PET) imaging in patients with suspected prostate cancer recurrence and non-informative bone scintigraphy, computerized tomography or magnetic resonance imaging.[Label]

Pharmacodynamics

Choline is phosphorylated by choline kinase into phosphorylcholine. This phosphorylated form gets trapped inside the cell. Cancer cells exhibit an increased cell wall membrane synthesis as well as an increased activity of choline kinase. Choline C11 presents a small tracer activity in the urinary collecting system and this property makes it a very noble compound in the evaluation of ureters and bladder.[3]

Mechanism of action

Choline is incorporated into phosphatidylcholine which is a major membrane phospholipid in mammalian cells. The use of choline C11 is based on the knowledge that malignant tumors with increased cellular proliferation take up more choline when compared with normal cells for the formation of cellular membranes.[1] The increased uptake of choline is explained by its use as a substrate in phospholipid synthesis in cell membranes, transmembrane signaling, and lipid and cholesterol transport and metabolism.[2]

Absorption

The highest normal tissue uptake is seen in renal cortex, liver, pancreas and salivary glands. It presents a variable bowel, prostate and pituitary uptake and a low uptake in the cerebral cortex. The short half-life of choline C11 limits the availability and it is recommended to be delivered within 2-3 half-lives from producing cyclotron.[5]

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Choline C11 is phosphorylated by choline kinase and incorporated into phospholipids in the body. In some of the tissues, choline oxidation is prominent. The oxidative metabolite of choline is betaine which is the major metabolite of choline C11. A small portion of the administered dose remains unchanged 40 minutes after administration.[5]

Route of elimination

Choline 11 presents a minimal urinary excretion and it represents <2% of the injected radioactivity.[2] After intravenous administration, choline C11 gets rapidly cleared from the circulation (<3 min) with a high clearance by liver and kidneys.[5] The oxidation metabolite of choline, named betaine, is excreted into the urine.[5]

Half life

The isotope half-life of choline C11 is 20.4 min.[2]

Clearance

After intravenous injection, choline C11 is rapidly cleared from the bloodstream. The clearance rate of choline C11 is or 0.014 ml/min.[5]

Toxicity

Choline is a natural compound with no known toxic effects at the levels administered in the form of choline C11. The carcinogenic effect of choline C11 has not been determined in long-term studies.[5]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
AcrivastineCholine C 11 may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
AdefovirAdefovir may decrease the excretion rate of Choline C 11 which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Chotipanich C, Kunawudhi A, Promteangtrong C, Tungsuppawattanakit P, Sricharunrat T, Wongsa P: Diagnosis of Hepatocellular Carcinoma Using C11 Choline PET/CT: Comparison with F18 FDG, ContrastEnhanced MRI and MDCT. Asian Pac J Cancer Prev. 2016;17(7):3569-73. [PubMed:27510010]
  2. Fox JJ, Schoder H, Larson SM: Molecular imaging of prostate cancer. Curr Opin Urol. 2012 Jul;22(4):320-7. doi: 10.1097/MOU.0b013e32835483d5. [PubMed:22617062]
  3. Welle CL, Cullen EL, Peller PJ, Lowe VJ, Murphy RC, Johnson GB, Binkovitz LA: (1)(1)C-Choline PET/CT in Recurrent Prostate Cancer and Nonprostatic Neoplastic Processes. Radiographics. 2016 Jan-Feb;36(1):279-92. doi: 10.1148/rg.2016150135. [PubMed:26761541]
  4. Krohn KA: Evaluation of alternative approaches for imaging cellular growth. Q J Nucl Med. 2001 Jun;45(2):174-8. [PubMed:11476167]
  5. Society of nuclear medicine and molecular imaging [Link]
External Links
PubChem Compound
14989482
PubChem Substance
310265171
ChemSpider
28514887
ChEBI
72321
ChEMBL
CHEMBL2095207
FDA label
Download (400 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Unknown StatusDiagnosticHepatocellular,Carcinoma1
3CompletedDiagnosticMetastatic Hormone Refractory Prostate Cancer1
Not AvailableAvailableNot AvailableProstate Cancer / Recurrent Prostate Cancer1
Not AvailableCompletedNot AvailableProstate Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble'Choline MSDS'
Radioactivity (mCi/mL)33'FDA label'
Predicted Properties
PropertyValueSource
Water Solubility5.45 mg/mLALOGPS
logP-4ALOGPS
logP-4.7ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)13.97ChemAxon
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity42.19 m3·mol-1ChemAxon
Polarizability12.57 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cholines. These are organic compounds containing a N,N,N-trimethylethanolammonium cation.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Quaternary ammonium salts
Direct Parent
Cholines
Alternative Parents
Tetraalkylammonium salts / 1,2-aminoalcohols / Primary alcohols / Organopnictogen compounds / Organic zwitterions / Organic chloride salts / Hydrocarbon derivatives
Substituents
Choline / Tetraalkylammonium salt / 1,2-aminoalcohol / Alkanolamine / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Organic chloride salt / Organic salt / Organic zwitterion
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
chloride salt, quaternary ammonium salt (CHEBI:72321)

Drug created on October 28, 2015 16:45 / Updated on November 02, 2018 07:01