Technetium Tc-99m oxidronate

Identification

Name
Technetium Tc-99m oxidronate
Accession Number
DB09139
Type
Small Molecule
Groups
Approved
Description

Technetium Tc-99m oxidronate, also known as 99mTc-methylene diphosphonate, is a radiopharmaceutical. A radiopharmaceutical is defined as a medicinal formulation containing radioisotopes that are used in major clinical areas for diagnosis and/or therapy.[2] The radiopharmaceuticals based on technetium-99m are widely used for diagnostic purposes because 99mTc has a versatile chemistry which allows it to produce an extense variety of complexes with specific characteristics.[3] These complexes are formed by the binding of 99mTc to metal atoms of an organic molecule. The group oxidronate falls into the category of diphosphonates whose structure allows them to bind to calcium.[4] Thus, technetium Tc-99m oxidronate is a powerful detection tool for abnormal osteogenesis by skeletal scintigraphy.[5] It was developed by Mallinkrodt nuclear and FDA approved on February 18, 1981.

Structure
Thumb
Synonyms
  • 99mtc-HDP
  • Oxidronic acid 99mtc-complex
  • Technetium (99mTc) oxidronate
  • Technetium 99mtc oxidronate
  • Technetium Tc 99m oxidronate
Categories
UNII
MG4KI49HHJ
CAS number
72945-61-0
Weight
Average: 290.906
Monoisotopic: 290.865131083
Chemical Formula
CH6O7P2Tc
InChI Key
SIJNDWFHVBDXDY-NLQOEHMXSA-N
InChI
InChI=1S/CH6O7P2.Tc/c2-1(9(3,4)5)10(6,7)8;/h1-2H,(H2,3,4,5)(H2,6,7,8);/i;1+2
IUPAC Name
[hydroxy(phosphono)methyl]phosphonic acid (⁹⁹Tc)technetium
SMILES
[99Tc].OC(P(O)(O)=O)P(O)(O)=O

Pharmacology

Indication

Technetium Tc-99m oxidronate is indicated in adult and pediatric patients to be used in skeletal imaging for diagnosis of areas that can present altered osteogenesis. When administered intravenously, it is able to generate a clear image of the bones which allows the physician to diagnose any bone problem.[6] It is important to point out that this drug has to be manipulated only under the service of a nuclear specialist.[5] The approved indications for a bone scan are 1) visualization of tumor metastasis in bone, 2) osteomyelitis, 3) fracture, 4) stress fracture, 5) avascular necrosis, 6) osteoporosis and 7) prosthetic joint evaluation. From all the major indications, the detection of a metastatic disease is the most common because it presents a 95% of sensitivity and lesion detection can be done 6 months earlier than with X-ray studies.[4]

Associated Conditions
Pharmacodynamics

The technetium is generated in a molibdene generator. Technetium Tc-99m presents a reduction of gamma emission after 6 hours and it is considered a quasi-stable molecule.[5] The visualization of bone lesions is possible since there is an altered uptake in areas of abnormal osteogenesis.[4] The principal photon used for detection is the gamma-2 with an energy of 140.5 keV.[5] Its use for bone examination should be performed 2 hours after initial injection with a recommended activity on the range of 370-740 MBq.[8]

Mechanism of action

The exact mechanism for bone uptake of technetium Tc-99m oxidronate is unknown. The most accepted mechanism is the localization of 99m-Tc on the surface of hydroxyapatite crystals of bone by chemisorption. Chemisorption is explained as a type of adsorption that involves a chemical reaction between the surface and the adsorbate in which new strong interactions form electronic bonds at the adsorbent surface.[1] The presented chemisorption are regulated by the blood flow and blood concentration because it restrains the delivery of the agent in the uptake sites.[4]

Absorption

Technetium Tc-99m oxidronate is rapidly absorbed and cleared from blood plasma to reach the skeleton.[7] After 27 min of intravenous administration, a range of 45-50% of the technetium Tc-99m oxidronate is accumulated in the skeleton, reaching maximum accumulation at 1-hour post injection and remaining constant until 72 hours postinjection.[8]

Volume of distribution

The distribution of technetium Tc-99m oxidronate at 1-hour post injection is mainly in the bones and secondary in the liver and kidneys.[3]

Protein binding

The protein binding has been reported to be around 20-30% after 2-3 hours of intravenous administration.[8]

Metabolism

Technetium Tc-99m oxidronate is a diphosphonate. There have been reports showing that diphosphonates form very stable Tc(IV) complexes which provide them with a very high in vivo stability and a very low degradation.[8]

Route of elimination

It is recommended to empty bladder completely just prior to technetium Tc-99m oxidronate administration. It is as well recommended to drink abundant water and to empty bladder as often as possible to reduce radiation exposure in the bladder wall. The total radioactivity in blood between 5 min and 24 hours goes from 40% to 2.3% respectively. Technetium Tc-99m oxidronate whole body retention after 24 hours is a ratio of 36.6% which indicates that this drug, unlike other bone radiopharmaceuticals, presents a greater uptake. The glomerular filtration of technetium Tc-99m oxidronate can reach a 60% of the administered dose after 6 hours of the initial dose. The cumulative activity excreted in the urine after 24 hours is of approximately 59% suggesting a ratio of femur-to-muscle of 35.[8]

Half life

The elimination of technetium Tc-99m oxidronate is marked by the presence of three different half-times which are: 1) rapid phase of 3.5 min, 2) intermediate phase of 27 min and 3) slow phase of 144 min.[8]

Clearance

During the first 24 hours of technetium Tc-99m oxidronate administration, it is observed a rapid clearance from blood and non-osseous tissues. The dosage gets accumulated in skeleton and urine.[7]

Toxicity

There has not been performed long-term animal studies to evaluate carcinogenic potential or an effect in fertility in males or females.[7]

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

Interactions

Drug Interactions
DrugInteraction
1,10-Phenanthroline1,10-Phenanthroline may decrease effectiveness of Technetium Tc-99m oxidronate as a diagnostic agent.
AbacavirAbacavir may decrease the excretion rate of Technetium Tc-99m oxidronate which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Technetium Tc-99m oxidronate which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Technetium Tc-99m oxidronate which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Technetium Tc-99m oxidronate which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Technetium Tc-99m oxidronate which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Technetium Tc-99m oxidronate which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Technetium Tc-99m oxidronate which could result in a higher serum level.
AcrivastineTechnetium Tc-99m oxidronate may decrease the excretion rate of Acrivastine which could result in a higher serum level.
ActeosideActeoside may decrease effectiveness of Technetium Tc-99m oxidronate as a diagnostic agent.
Food Interactions
Not Available

References

General References
  1. Oura K., Lifshits G., Saranin A., Zotov V. and Katayama M. (2003). Surface science, an introduction. Springer.
  2. WHO [Link]
  3. IAEA [Link]
  4. Human health IAEA [Link]
  5. Doctissimo [Link]
  6. Pubmedhealth [Link]
  7. SNMjournals [Link]
  8. Tc-99m compounds [Link]
External Links
KEGG Drug
D06041
PubChem Compound
123801
PubChem Substance
347827826
ATC Codes
V09BA01 — Technetium (99mtc) oxidronic acid
FDA label
Download (118 KB)
MSDS
Download (44.2 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
melting point (°C)0ºC (reconstituted)'MSDS'
boiling point (°C)100ºC (reconstituted)'MSDS'
water solubilitySoluble'MSDS'
Radioactivity (mCi/mL)100000'MSDS'
Predicted Properties
PropertyValueSource
Water Solubility13.5 mg/mLALOGPS
logP-1.1ALOGPS
logP-2ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)0.75ChemAxon
pKa (Strongest Basic)-5ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area135.29 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity29.72 m3·mol-1ChemAxon
Polarizability11.94 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
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 bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic phosphonic acids and derivatives
Sub Class
Bisphosphonates
Direct Parent
Bisphosphonates
Alternative Parents
Organic phosphonic acids / Organic transition metal salts / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Bisphosphonate / Organophosphonic acid / Organic transition metal salt / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organic salt / Organophosphorus compound / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
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. Tc-99m compounds [Link]

Drug created on September 30, 2015 10:50 / Updated on November 02, 2018 06:59