Technetium Tc-99m tetrofosmin

Identification

Name
Technetium Tc-99m tetrofosmin
Accession Number
DB09160  (DB09505)
Type
Small Molecule
Groups
Approved
Description

Technetium Tc-99m tetrofosmin is a drug used in nuclear myocardial perfusion imaging. The radioisotope, technetium-99m, is chelated by two 1,2-bis[di-(2-ethoxyethyl)phosphino]ethane ligands which belong to the group of diphosphines and which are referred to as tetrofosmin. It is a lipophilic technetium phosphine dioxo cation that was formulated into a freeze-dried kit which yields an injection.[1] Technetium Tc-99m tetrofosmin was developed by GE Healthcare and FDA approved on February 9, 1996.

Structure
Thumb
Synonyms
  • Tc-99m tetrofosmin
  • Technetium (99mTc) tetrofosmin
  • Technetium Tc 99m tetrofosmin
  • Technetium-99 tetrofosmin
External IDs
PPN-1011
Categories
UNII
42FOP1YX93
CAS number
127455-27-0
Weight
Average: 898.86
Monoisotopic: 898.408712589
Chemical Formula
C36H84O10P4Tc
InChI Key
HBJYDUADMKVTGP-RCUQKECRSA-N
InChI
InChI=1S/2C18H40O4P2.2H2O.Tc/c2*1-5-19-9-13-23(14-10-20-6-2)17-18-24(15-11-21-7-3)16-12-22-8-4;;;/h2*5-18H2,1-4H3;2*1H2;/i;;;;1+1
IUPAC Name
bis(6,9-bis(2-ethoxyethyl)-3,12-dioxa-6,9-diphosphatetradecane) (⁹⁸Tc)technetium dihydrate
SMILES
O.O.[98Tc].CCOCCP(CCOCC)CCP(CCOCC)CCOCC.CCOCCP(CCOCC)CCP(CCOCC)CCOCC

Pharmacology

Indication

Technetium-99m tetrofosmin is indicated for the diagnosis of heart abnormalities by exercise myocardial scintigraphy. The exercise myocardial scintigraphy is an established method for the diagnosis of the severity of coronary artery disease.[1] This method allows distinguishing regions of reversible myocardial ischemia in the presence or absence of infarcted myocardium following rest and stress conditions.[4] The use of technetium-99m tetrofosmin is mainly used to assess myocardial perfusion in ischemia and infarction.[3]

Pharmacodynamics

Preclinical studies have reported that technetium-99m tetrofosmin presents a very good heart uptake and retention. The diagnosis based on the presence of technetium-99m is considered to have a principal photon gamma emissions at 140.5 keV.[3] The imaging can be done at 15 minutes after stress and 30-60 minutes at rest but, due to its slow wash out from myocardium, it is possible to perform imaging for up to 4 hours post-injection.[4] Administration of technetium-99m tetrofosmin generates a count elevation in white blood cell at 6-24 hours post-injection.[1]

Mechanism of action

The mechanism for the uptake and retention of technetium-99m tetrofosmin is not well established. Nonetheless, it is known that technetium 99m tetrofosmin binds to the intracellular cytosol of myocytes.[3] This uptake is thought to be because technetium-99m tetrofosmin is a lipophilic cationic agent which allows it to present a passive diffusion process. Once the uptake is done, the technetium-99m accumulates in viable myocardial tissue delineating the infarcts areas when administered at rest and delineating the ischemic areas when administered at stress.[3]

Absorption

After intravenous admministration, technetium 99m tetrofosmin is taken up in the heart where the uptake is done by potential-driven diffusion of the lipophilic cationic complex accross the sarcolemmal and mitochondrial membranes.[3] The uptake in myocardium represents approximately 1.2% of the administered activity after 5 minutes of injection and this activity reduces to 1% at 2 hours. Once taken by the myocardium, there is a minimal redistribution in the following 3-4 hours.[4]

Volume of distribution

Reports have shown that it is possible to perform heart diagnosis and analysis as early as 5 minutes post-injection.[1] After absorption, technetium-99m tetrofosmin is accumulated in the myocardium, skeletal muscle, liver, spleen and kidneys. If administered during exercise, there is a sequestration of technetium-99m tetrofosmin by skeletal muscle due to increased flow in skeletal tissue.[4]

Protein binding

The protein binding of technetium-99m tetrofosmin has not been assessed, but it is thought that the uptake of this drug may be related to its binding to P-glycoprotein and multidrug resistance proteins.[2]

Metabolism

The liver activity post injection of technetium-99m tetrofosmin is very low and it decays over time.[4]

Route of elimination

The elimination of technetium-99m tetrofosmin is roughly the same for both fecal and urinary excretion and both account for apporximately 50% of the total excreted dose.[1] The washout from the heart is slow and it depends on the patient state being of 4% per hour at exercise and 0.6% at rest.[3] Complete elimination occurs after 48 hours. In this process, renal clearance accounts for approximately 40% of the administered dose in both rest and excercise; while fecal clearance accounts for 26-41% of the administered dose at rest and 17-34% of the administered dose after exercise.[4]

Half life

Technetium-99m tetrofosmin presents a very short half-life of 6.03 hours which is an advantage over other labeled radiopharmaceuticals.[1]

Clearance

Technetium-99m tetrofosmin has a rapid clearance from the liver, lung and blood. The whole body clearance after 48 hours represents approximately 70% of the administered dose. Blood and plasma clearance follows an equal clearance profile in which at 10 min post injection there was less than 5% of the initial administered dose. The initial rate of urinary clearance accounts for 40% of the administered dose after 48 hours of the initial dose administration.[1]

Toxicity

Technetium-99m tetrofosmin has a very high safety margin in both single and repeated dose intravenous administration. It does not exhibit mutagenic potential in vitro and in vivo.[1] Reports have shown that technetium-99m tetrofosmin can cross the placenta thus, the possibility of pregnancy should be assessed.[4]

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

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Higley B, Smith FW, Smith T, Gemmell HG, Das Gupta P, Gvozdanovic DV, Graham D, Hinge D, Davidson J, Lahiri A: Technetium-99m-1,2-bis[bis(2-ethoxyethyl) phosphino]ethane: human biodistribution, dosimetry and safety of a new myocardial perfusion imaging agent. J Nucl Med. 1993 Jan;34(1):30-8. [PubMed:8418268]
  2. Jadvar H. (2014). Cancer theranostics. Academic press.
  3. Technetium radiopharmaceutical chemistry [Link]
  4. Monograph [Link]
External Links
KEGG Drug
D06050
PubChem Compound
131704316
PubChem Substance
310265073
ATC Codes
V09GA02 — Technetium (99mtc) tetrofosmin
FDA label
Download (222 KB)
MSDS
Download (73 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)100ºC'MSDS'
water solubilitySoluble'MSDS'
Predicted Properties
PropertyValueSource
Water Solubility0.000664 mg/mLALOGPS
logP3.85ALOGPS
logP1.14ChemAxon
logS-5.8ALOGPS
pKa (Strongest Basic)8.3ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area36.92 Å2ChemAxon
Rotatable Bond Count38ChemAxon
Refractivity115.73 m3·mol-1ChemAxon
Polarizability45.52 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as organic phosphines and derivatives. These are organic compounds containing a phosphine derivative, with the general formula B1P(R2)R3 (R1-R3=alkyl, aryl).
Kingdom
Organic compounds
Super Class
Organophosphorus compounds
Class
Organic phosphines and derivatives
Sub Class
Not Available
Direct Parent
Organic phosphines and derivatives
Alternative Parents
Organic transition metal salts / Dialkyl ethers / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Phosphine / Organic transition metal salt / Ether / Dialkyl ether / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organic salt / Organooxygen compound
Molecular Framework
Not Available
External Descriptors
Not Available

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Jadvar H. (2014). Cancer theranostics. Academic press.

Drug created on October 02, 2015 14:10 / Updated on November 02, 2018 06:59