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Chemistry

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Also known as: Technescan hdp, Oxidronic acid 99mtc-complex, Technetium tc-99m oxidronate, 99mtc-hdp, Mg4ki49hhj, 72945-61-0
Molecular Formula
CH6O7P2Tc
Molecular Weight
290.91  g/mol
InChI Key
SIJNDWFHVBDXDY-IEOVAKBOSA-N
FDA UNII
MG4KI49HHJ

Technetium Hmdp
Technetium Tc-99m oxidronate, also known as 99mTc-methylene diphosphonate, is a radiopharmaceutical agent. A radiopharmaceutical is defined as a medicinal formulation containing radioisotopes that are used in major clinical areas for diagnosis and/or therapy. 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. 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. Thus, technetium Tc-99m oxidronate is a powerful detection tool for abnormal osteogenesis by skeletal scintigraphy. It was developed by Mallinkrodt nuclear and FDA approved on February 18, 1981.
Technetium tc-99m oxidronate is a Radioactive Diagnostic Agent. The mechanism of action of technetium tc-99m oxidronate is as a Radiopharmaceutical Activity.
1 2D Structure

Technetium Hmdp

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
[hydroxy(phosphono)methyl]phosphonic acid;technetium-99
2.1.2 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+1
2.1.3 InChI Key
SIJNDWFHVBDXDY-IEOVAKBOSA-N
2.1.4 Canonical SMILES
C(O)(P(=O)(O)O)P(=O)(O)O.[Tc]
2.1.5 Isomeric SMILES
C(O)(P(=O)(O)O)P(=O)(O)O.[99Tc]
2.2 Other Identifiers
2.2.1 UNII
MG4KI49HHJ
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Osteoscan

2. Tc-99m Hydroxymethylene Diphosphonate

3. Tc-99m-hdp

4. Tc-99m-hmdp

5. Tc-99m-oxidronate

6. Technetium Hmdp

7. Technetium Osteoscan-hdp

8. Technetium Salt (hydroxymethylene)bis(phosphonic Acid)

9. Technetium Tc 99m Hydroxymethylene Diphosphonate

2.3.2 Depositor-Supplied Synonyms

1. Technescan Hdp

2. Oxidronic Acid 99mtc-complex

3. Technetium Tc-99m Oxidronate

4. 99mtc-hdp

5. Mg4ki49hhj

6. 72945-61-0

7. Technetium 99mtc Oxidronate

8. Technetium Hmdp

9. [hydroxy(phosphono)methyl]phosphonic Acid;technetium-99

10. Phosphonic Acid, (hydroxymethylene)bis-, Technetium-99tc Salt

11. Tc-99m-oxidronate

12. Tc-99m-hmdp

13. Tc-99m-hdp

14. Technetium Osteoscan-hdp

15. Unii-mg4ki49hhj

16. Technescan

17. Tc-99m Hydroxymethylene Diphosphonate

18. Technetium-99mtc-methylene Diphosphonate

19. Technetium Tc 99m Methylene Diphosphonate

20. Technetium Tc 99m Hydroxymethylene Diphosphonate

21. Technetium (99mtc) Oxidronate

22. Technetium Salt (hydroxymethylene)bis(phosphonic Acid)

23. Db09139

24. Technetium Tc-99m Oxidronate Kit

25. Oxidronic Acid 99mtc-complex [mi]

26. Technetium Tc 99m Oxidronate [who-dd]

27. Technetium Tc 99m Oxidronate [usp Impurity]

28. Q22075854

2.4 Create Date
2005-08-08
3 Chemical and Physical Properties
Molecular Weight 290.91 g/mol
Molecular Formula CH6O7P2Tc
Hydrogen Bond Donor Count5
Hydrogen Bond Acceptor Count7
Rotatable Bond Count2
Exact Mass290.865126 g/mol
Monoisotopic Mass290.865126 g/mol
Topological Polar Surface Area135 Ų
Heavy Atom Count11
Formal Charge0
Complexity174
Isotope Atom Count1
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count2
4 Drug and Medication Information
4.1 Drug 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. It is important to point out that this drug has to be manipulated only under the service of a nuclear specialist. 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.


FDA Label


5 Pharmacology and Biochemistry
5.1 Pharmacology

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. The visualization of bone lesions is possible since there is an altered uptake in areas of abnormal osteogenesis. The principal photon used for detection is the gamma-2 with an energy of 140.5 keV. Its use for bone examination should be performed 2 hours after initial injection with a recommended activity on the range of 370-740 MBq.


5.2 MeSH Pharmacological Classification

Radiopharmaceuticals

Compounds that are used in medicine as sources of radiation for radiotherapy and for diagnostic purposes. They have numerous uses in research and industry. (Martindale, The Extra Pharmacopoeia, 30th ed, p1161) (See all compounds classified as Radiopharmaceuticals.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
TECHNETIUM TC-99M OXIDRONATE
5.3.2 FDA UNII
MG4KI49HHJ
5.3.3 Pharmacological Classes
Mechanisms of Action [MoA] - Radiopharmaceutical Activity
5.4 Absorption, Distribution and Excretion

Absorption

Technetium Tc-99m oxidronate is rapidly absorbed and cleared from blood plasma to reach the skeleton. 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.


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.


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.


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.


5.5 Metabolism/Metabolites

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.


5.6 Biological 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.


5.7 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. The presented chemisorption are regulated by the blood flow and blood concentration because it restrains the delivery of the agent in the uptake sites.


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