Sodium pertechnetate is the inorganic compound

Inorganic compound

Inorganic compounds have traditionally been considered to be of inanimate, non-biological origin. In contrast, organic compounds have an explicit biological origin. However, over the past century, the classification of inorganic vs organic compounds has become less important to scientists,...

 with the formula NaTcO₄. This colourless salt consists of the anion [TcO₄]⁻. The radioactive ^99mTcO₄⁻ anion is an important radiopharmaceutical for diagnostic

Medical diagnosis

Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

 use. The advantages to ^99mTc include its short half-life

Half-life

Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 of 6 hours and the low radiation exposure to the patient, which allow a patient to be injected with activities of more than 30 millicuries. Na[^99mTcO₄] is a precursor to a variety of derivatives that are used to image different parts of the body.

Chemistry

[TcO₄]⁻ is the starting material for most of the chemistry of technetium. Pertechnetate salts are usually colorless. [TcO₄]⁻ is produced by oxidizing technetium with nitric acid or with hydrogen peroxide. The pertechnetate anion is similar to the permanganate

Permanganate

A permanganate is the general name for a chemical compound containing the manganate ion, . Because manganese is in the +7 oxidation state, the permanganate ion is a strong oxidizing agent. The ion has tetrahedral geometry...

 anion but is a weaker oxidizing agent

Oxidizing agent

An oxidizing agent can be defined as a substance that removes electrons from another reactant in a redox chemical reaction...

. It is tetrahedral and diamagnetic. The standard electrode potential for TcO₄⁻/TcO₂ is only +0.738 V in acidic solution, as compared to +1.695 V for MnO₄⁻/MnO₂. Because of its diminished oxidizing power, [TcO₄]⁻ is stable in alkaline solution. [TcO₄]⁻ is more similar to ReO₄⁻. Depending of the reducing agent, [TcO₄]⁻ can be converted to derivatives containing Tc(VI), Tc(V), and Tc(IV). In the absence of strong complexing ligands, TcO₄⁻ is reduced to a +4 oxidation state via the formation of TcO₂ hydrate.

Pharmaceutical use

The half-life of ^99mTc is long enough that labelling synthesis of the radiopharmaceutical and scintigraphic measurements can be performed without significant loss of radioactivity. The energy emitted from ^99mTc is 140 keV, which allows for the study of deep body organs. Radiopharmaceuticals have no intended pharmacologic effect and are used in very low concentrations. Radiopharmaceuticals containing ^99mTc are currently being applied in the determining morphology of organs, testing of organ function, and scintigraphic and emission tomographic imaging. The gamma radiation emitted by the radionuclide allows organs to be imaged in vivo tomographically. Currently, over 80% of radiopharmaceuticals used clinically are labelled with ^99mTc. A majority of radiopharmaceuticals labelled with ^99mTc are synthesized by the reduction of the pertechnetate ion in the presence of ligands chosen to confer organ specificity of the drug. The resulting ^99mTc compound is then injected into the body and a "gamma camera" is focused on sections or planes in order to image the spacial distribution of the ^99mTc.

Specific imaging applications

^99mTc is used primarily in the study of the thyroid gland - its morphology, vascularity, and function. [TcO₄]⁻ and iodide

Iodide

An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. This page is for the iodide ion and its salts. For information on organoiodides, see organohalides. In everyday life, iodide is most commonly encountered as a component of iodized salt,...

, due to their comparable charge/radius ratio, are similarly incorporated into the thyroid gland. The pertechnetate ion is not incorporated into the thyroglobulin

Thyroglobulin

Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

. It is also used in the study of blood perfusion, regional accumulation, and cerebral lesions in the brain, as it accumulates primarily in the choroid plexus

Choroid plexus

The choroid plexus is a structure in the ventricles of the brain where cerebrospinal fluid is produced...

.

Sodium pertechnetate cannot pass through the blood-brain barrier

Blood-brain barrier

The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

. In addition to the salivary and thyroid glands, ^99mTcO₄⁻ localizes in the stomach. ^99mTcO₄⁻ is renally eliminated for the first three days after being injected. After a scanning is performed, it is recommended that a patient drink large amounts of water in order to expedite elimination of the radionuclide. Other methods of ^99mTcO₄⁻ administration include intraperitoneal, intramuscular, subcutaneous, as well as orally. The behavior of the ^99mTcO₄⁻ ion is essentially the same, with small differences due to the difference in rate of absorption, regardless of the method of administration.

Other examples of organ-specific radiopharmaceuticals include:

Preparation of ^99mTcO₄⁻

^99mTc is conveniently available in high radionuclidic purity from molybdenum

Molybdenum

Molybdenum , is a Group 6 chemical element with the symbol Mo and atomic number 42. The name is from Neo-Latin Molybdaenum, from Ancient Greek , meaning lead, itself proposed as a loanword from Anatolian Luvian and Lydian languages, since its ores were confused with lead ores...

-99, which decays with 87% probability to ^99mTc. The subsequent decay of ^99mTc leads to either ⁹⁹Tc or ⁹⁹Rb. ⁹⁹Mo can be produced in a nuclear reactor via irradiation

Irradiation

Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serve a specific purpose, rather than radiation exposure to...

 of either molybdenum-98 or naturally occurring molybdenum with thermal neutrons, but this is not the method currently in use today. Currently, ⁹⁹Mo is recovered as a product of the nuclear fission reaction of ²³⁵U, separated from other fission products via a multistep process and loaded onto a column of alumina that forms the core of a ⁹⁹Mo/^99mTc radioisotope "generator".

As the ⁹⁹Mo continuously decays to ^99mTc, the ^99mTc can be removed periodically (usually daily) by flushing a saline solution (0.15 M NaCl in water) through the alumina column: the more highly charged ⁹⁹MoO₄²⁻ is retained on the column, where it continues to undergo radioactive decay, while the medically useful radioisotope ^99mTcO₄⁻ is eluted in the saline. The eluate from the column must be sterile and pyrogen free, so that the Tc drug can be used directly, usually within 12 hours of elution. In a few cases, sublimation or solvent extraction may be used.

Synthesis of ^99mTcO₄⁻ radiopharmaceuticals

^99mTcO₄⁻ is advantageous for the synthesis of a variety of radiopharmaceuticals because Tc can adopt a number of oxidation states. The oxidation state and coligands dictate the specificity of the radiopharmaceutical. The starting material Na^99mTcO₄, made available after elution from the generator column, as mentioned above, can be reduced in the presence of complexing ligands. Many different reducing agents can be used, but transition metal reductants are avoided because they compete with ^99mTc for ligands. Oxalates, formates, hydroxylamine, and hydrazine are also avoided because they form complexes with the technetium. Electrochemical reduction is impractical.

Ideally, the synthesis of the desired radiopharmaceutical from ^99mTcO₄⁻, a reducing agent, and desired ligands should occur in one container after elution, and the reaction must be performed in a solvent that can be injected intravenously, such as a saline solution. Kits are available that contain the reducing agent, usually tin(II) and ligands. These kits are sterile, pyrogen-free, easily purchased, and can be stored for long periods of time. The reaction with ^99mTcO₄⁻ takes place directly after elution from the generator column and shortly before its intended use. A high organ specificity is important because the injected activity should accumulate in the organ under investigation, as there should be a high activity ratio of the target organ to nontarget organs. If there is a high activity in organs adjacent to the one under investigation, the image of the target organ can be obscured. Also, high organ specificity allows for the reduction of the injected activity, and thus the exposure to radiation, in the patient. The radiopharmaceutical must be kinetically inert, in that it must not change chemically in vivo en route to the target organ.

Examples

• A complex that can penetrate the blood-brain barrier is generated by reduction of ^99mTcO₄⁻ with tin(II) in the presence of the ligand "d,l-HMPAO" to form TcO-d,l-HMPAO (HM-PAO is hexamethylpropyleneamino oxime
  Oxime
  An oxime is a chemical compound belonging to the imines, with the general formula R1R2C=NOH, where R1 is an organic side chain and R2 may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted oximes form a closely related family of compounds...
  
  ).
• A complex that for imaging the lungs, "Tc-MAA," is generated by reduction of ^99mTcO₄⁻ with SnCl₂ in the presence of human serum albumin.
• [^99mTc(OH₂)₃(CO)₃]⁺, which is both water and air stable, is generated by reduction of ^99mTcO₄⁻ with carbon monoxide. This compound is a precursor to complexes that can be used in cancer diagnosis and therapy involving DNA-DNA pretargeting.

Other reactions involving the pertechnetate ion

• Radiolysis of TcO₄⁻ in nitrate solutions proceeds through the reduction to TcO₄²⁻ which induces complex disproportionation processes:

TcO₄⁻ + e⁻ → TcO₄²⁻

2 TcO₄²⁻ → TcO₄⁻ + Tc(V)

2 Tc(V) → TcO₄²⁻ + Tc(IV)

Tc(V) + TcO₄²⁻ → Tc(IV) + TcO₄⁻

• Pertechnetate can be reduced by H₂S
  Hydrogen sulfide
  Hydrogen sulfide is the chemical compound with the formula . It is a colorless, very poisonous, flammable gas with the characteristic foul odor of expired eggs perceptible at concentrations as low as 0.00047 parts per million...
  
  to give Tc₂S₇.¹⁰
• Pertechnetate is also be reduced to Tc(IV/V) compounds in alkaline solutions in nuclear waste tanks without adding catalytic metals, reducing agents, or external radiation. Reactions of mono- and disaccharides with ^99mTcO₄⁻ yield Tc(IV) compounds that are water soluble.