Loyola University Medical Education Network

Tc-99m Radiopharmaceuticals


Sodium pertechnetate may be used "as is" after elution from the Mo/Tc Generator and is the only Tc-99m compound that requires no manipulation on the part of Nuclear Medicine personnel. It may be injected intravenously, used to label blood cells or other molecules for intravenous injection, or bound to molecules suitable for oral administration.

The majority of Tc-99m compounds employ the stannous reduction method, which makes use of the fact that stannous chloride is one of the most powerful reducing agents available to chemists. Tc-99m obtained from the Mo/Tc generator is in the chemical form of TcO4-, or pertechnetate. While the anion has an overall negative charge of -1, the oxidation number of the Tc is 7+. The chelating agents commonly used to prepare Tc-99m products are also anions with an overall negative charge due to the presence of N, O, and P atoms, each of which has 1 or more extra pairs of electrons. These negative charges repel each other so pertechnetate will not form chelates. A reducing agent is therefore required to convert the Tc-99m into an electropositive cationic form capable of binding to chelating agents. Tc-99m sulfur colloid and Tc-99m DMSA are the only 2 commercially available Tc-99m compounds that do not use the stannous reduction method.

The following reduction/oxidation reactions (REDOX) indicate that the pertechnetate is typically reduced to Tc4+ while the stannous ion (Sn2+) is converted to stannic ion (Sn4+). In the overall reaction, the stannous ion is the reducing agent, and therefore the substance oxidized, while pertechnetate is the oxidizing agent and therefore the substance reduced.

3 Sn2+ - 6e- ---> 3Sn4+

2TcO4- + 16H+ + 6 e- ---> 2Tc4+ + 8H2O

Overall, 3Sn2+ + 2TcO4- + 16H+ ---> 3Sn4+ + 2Tc4+ + 8H2O

The Tc4+ is now in the appropriate chemical form to react with an anion like PYP, MDP, or DTPA. The complex formed is known as a chelate; the generic equation is shown below. Tc4+ + chelating agent n -----> Tc-chelate. For example,

Tc4+ + pyrophosphate 4- ----> Tc-pyrophosphate

Most soluble Tc-99m compounds, excluding those containing a protein, have octahedral structures and are said to be hexa-coördinated since there are typically 6 binding sites available consisting of N, O, or P atoms. An octahedral structure is shown in Figure 3. In the diagram, Mn+ represents a radiometal ion with a net positive charge due to the loss of n electrons. Certain compounds, e.g., the porphyrins, have a square planar array of N atoms in their center and are tetra-coördinated. Iron atoms bound to the heme portion of the hemoglobin molecule are located within the square planar array of nitrogen atoms (see Figure). In most kits, the desired molecule is already present and it is a simple matter of binding the reduced Tc-99m to the molecule. In the case of MAG3 and teboroxime, however, the desired molecule is actually formed during the first part of a 10 min heating cycle and this molecule then binds to the reduced Tc to form the Tc-chelate. This reaction requires the presence of the correct precursors in the reaction vial at the right concentration to produce the desired product.

Tc-99m reactions by the Thiol Reduction Method also result in complex formation. In this reaction, two thiol groups (-SH) lose their H-atoms and link together to form a disulfide bridge, comparable to the cystine/cysteine reactions. This is the reduction method used in the formation of Tc-99m DMSA, shown in the following reaction. The Tc-99m is trapped within the 4-member ring structure or between the SS bonds in two molecules of Tc-DMSA.

Tc-99m sulfur colloid is formed by the acid-catalyzed conversion of soluble thiosulfate ion to an insoluble Tc-99m heptasulfide, which coprecipitates with colloidal sulfur. Sodium thiosulfate solution is mixed with a small volume of 1 N hydrochloric acid and pertechnetate is then added to the mixture, which is shaken to insure homogeneity. The mixture is then heated at 100oC for 5-10 min depending upon manufacturer. Alternatively, it may be heated in a microwave oven for 12-25 sec depending upon the particular oven and the power level selected. At the end of the heating cycle, a small volume of a sodium acetate buffer is added to the reaction mixture to raise the pH to approximately 5.5. The Tc-SC is then cooled prior to quality control testing and injection.


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Stephen Karesh, PhD.

Last Updated: August 14, 1996
Created: March 1, 1996