Sodium pertechnetate

Sodium pertechnetate (sodium tetraoxotechnetate (VII)), [TcO₄]^-, is an ionic salt of sodium and pertechnetate. ^99mTcO₄^- is the basis of a family of radioactive pharmaceuticals approved for diagnostic use. The advantages to ^99mTc include its short half-life of 6 hours, low radiation exposure to the patient, and ability to effectively detect emitted gamma radiation. The short half-life of ^99mTc and the absence of radiation damage to tissues allow a patient to be injected with activities of more than 30 milliCuries. However, the half-life is long enough that labelling synthesis of the radiopharmaceutical and scintigraphic measurements can be performed without losing much activity. The energy emitted from ^99mTc is 140 keV, which allows for the study of deep body organs. The pertechnetate ion is primarily used in thyroid imaging because [TcO₄]^- and iodide, due to similar charge/radius ratio, are similarly incorporated into the thyroid gland. However, the pertechnetate ion is not incorporated into the thyroglobulin.^[1]

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Chemistry

[TcO₄]^-, the only tetrahedral oxoanion of technetium, is the basic starting material for all technetate chemistry. Pertechnetate salts are usually colorless.^[2] [TcO₄]^- is produced by oxidizing technetium with nitric acid, hydrogen peroxide. The pertechnetate anion is similar to the permanganate anion but is a weaker oxidizing agent. The standard electrode potential for TcO₄^-/TcO₂ is only +0.738 V in acidic solution, as compared to +1.695 V for MnO₄^-/MnO₂.^[1] Because of its diminished oxidizing powers, [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).^[3] In the absence of strong complexing ligands, TcO₄^- is reduced to a +4 oxidation state via the formation of TcO₂ hydrate.^[1]

Pharmaceutical use^[1]

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.

^99mTc is used primarily in the study of the thyroid gland - its morphology, vascularity, and function. 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. Sodium pertechnetate cannot pass through the blood-brain barrier but can be used when this barrier is damaged. ^99mTcO₄^- is not organically bound to the target organs of the body. Once sodium pertechnetate is injected into the body, it becomes localized in the salivary and thyroid glands, and the stomach. ^99mTcO₄^- is rapidly renally eliminated for the first three days after being injected. After a scanning is performed, it is recommended that a patient drink a large amount of water in order to expedite elimination of the technetium radionuclide.^[4] 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.^[5]

Preparation of ^99mTcO₄^-

^99mTc is made readily and conveniently available in high nuclidic purity through the decay of molybdenum-99, which decays with 87% probability to ^99mTc. The subsequent decay of ^99mTc leads to either ⁹⁹Tc or ⁹⁹Rb. ⁹⁹Mo is obtained in a nuclear reactor via irradiation of either molybdenum-98 or naturally occurring molybdenum with thermal neutrons. ^99mTc is also obtained by the fission of ²³⁵U or ²³⁹Pu,^[6] but the isolation of ^99mTc requires many steps due to the presence of other fission products and transuranium elements.^[1]

Once ^99mTc is formed, it can be separated from ⁹⁹Mo by column chromatography. In a few cases, sublimation or solvent extration may be used. The pertechnetate ion is formed by using acidic aluminum oxide as the packing material for the column. At the top of the column is bound ⁹⁹MoO₄^2-. ^99mTcO₄^- is extracted from the column by washing with a 0.15 M NaCl (" saline solution"). The eluate from the column must be sterile and pyrogen free, so that the Tc drug can be used directly, usually within 12 h of elution.^[1]

Synthesis of ^99mTcO₄^- radiopharmaceuticals^[1]

^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 for the synthesis of radiopharmaceuticals is Na^99mTcO₄, made available after elution from the generator column, as mentioned above. The Na^99mTcO₄^- 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 also complex with the ^99mTc. Electrochemical reduction of ^99mTcO₄^- is avoided in clinical practice because it requires excessive equipment.

Examples of organ specific radiopharmaceuticals include:

• A technetium complex that can penetrate the blood-brain barrier in which ^99mTcO₄^- reduced with tin (II) in the presence of the ligand d, l-HM-PAO to form TcO-d, l-HM-PAO (HM-PAO is hexamethylpropyleneamino oxime).
• A technetium complex that is used to image the lungs, Tc-MAA, is formed from the reduction of ^99mTcO₄^- with SnCl₂ in the presence of human serum albumin.
• [^99mTc(OH₂)₃(CO)₃]⁺, which is both water and air stable, can be directly synthesized from ^99mTcO₄^- in saline under 1 atm of CO. This compound can be easily substituted with various biomolecules, allowing this compound to be a precursor to complexes that can be used in cancer diagnosis and therapy involving DNA-DNA pretargeting.^[7]

Ideally, the synthesis of the desired radiopharmaceutical from ^99mTcO₄^-, a reducing agent, and desired ligands should occur in one step 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 highly 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.

Other reactions involving the pertechnetate ion

• Radiolysis of TcO₄^- in nitrate solutions proceeds through the reduction to TcO₄^2- which induces complex disproportionation processes:

TcO₄^- + e_aq^- → TcO₄^2-

2TcO₄^2- → TcO₄^- + Tc(V)

2Tc(V) → TcO₄^2- + Tc(IV)

Tc(V) + TcO₄^2- → Tc(IV) + TcO₄^-

• Pertechnetate can be reduced by H₂S 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.^[8]

References