**5. Chemistry of 99mTc and oxidation state for labeling**

Technetium belongs to transition metal family; its electronic configuration and physical properties are shown in table given below (**Table 4**). There are 22 isotopes of the technetium, but none of them is stable in nature. Half-life of 99Tc is 0.25 million years in its ground state. Oxidation state of technetium varies from 3 to +7 as shown in **Table 4** below. This happens due to the 4d and 5s loss or gain of

*Single-Photon Emission Computed Tomography (SPECT) Radiopharmaceuticals DOI: http://dx.doi.org/10.5772/intechopen.93449*


#### **Table 4.**

• Free from α and β particles emission (with little emission)

• Chemically reactive to form coordinate covalent bonds with the compound

Common properties of γ-emitting radionuclides for SPECT imaging are given in

More than 85% of radiopharmaceuticals which are being used to diagnose the cancer and infection are 99mTc labeled. The reason for using the 99mTc is due to

• Half-life of technetium is 6 hours which is sufficient to examine the catabolic as well as anabolic processes which occur in patient and minimal radiation

• Energy of the γ-rays emitted by technetium is very low (140 keV) which does not greatly damage the soft tissues of the patient body, although they have low

energy but can be detected by any sensitive gamma camera [7].

• Technetium is very reactive to make complex with compounds.

• Its short half-life enables us to get the imaging information very quickly.

• Decay of technetium takes place through isomeric transitions due to which electrons and gamma radiation of low energy is emitted. Therefore, beta

• Due to the emission of same energy levels of gamma radiation, the detector

changed according to the desired targeted body organ and parts, which makes it possible to develop a biological technetium labeled compound which can accumulate in high amount on that targeted organ and part of body which is

Technetium belongs to transition metal family; its electronic configuration and physical properties are shown in table given below (**Table 4**). There are 22 isotopes of the technetium, but none of them is stable in nature. Half-life of 99Tc is 0.25 million years in its ground state. Oxidation state of technetium varies from 3 to +7 as shown in **Table 4** below. This happens due to the 4d and 5s loss or gain of

• Most important property of technetium is that its oxidation state can be

alignment becomes very accurate as no beta radiation is emitted.

**5. Chemistry of 99mTc and oxidation state for labeling**

• Its excretion rate from the patient body is very fast.

radiation exposure to patent is negligible.

under investigation [8].

**6**

• Biological half-life not greater than time of study

**4. Characteristic of technetium-99m for labeling**

• Suitable energy range

which is to be labeled

following characteristics:

exposure time to the patients [6].

**Table 3**.

*Medical Isotopes*

*Physical and chemical properties of technetium.*

electrons by 4d orbital. Different types of ligands which are used to label the technetium and chemical conditions under which labeling process is accomplished are responsible for steadiness of such types of oxidation state. It is observed that technetium is found in nature in the form of halides (TcF6, TcCl6 and TcBr4, oxide, [TcO2, Tc2O7], sulfides [Tc2S7], and pertechnetate 99mTcO4 � in +4 to +7 oxidation states). Oxidation states of smaller values such as �1, +2, +3 are naturally stabilized during complex formation with varieties of ligands; for example, +3 oxidation state is stabilized by the chelating agent, methylene diphosphate [9]. Without the use of these chelating agents in complex formation, the oxidation state will not remain constant and technetium would oxidize to +4 oxidation state and eventually change to +7 oxidation state which is most stable state in complex. The +5 and +6 oxidation of technetium is habitually charged to +4 and +7 oxidation states as shown in the following Eqs. 1 and 2 which is most stable regardless of their proportion.

$$\mathbf{3Tc}^{+5} \ 2\mathbf{Tc}^{+4+} \ \mathbf{Tc}^{+7} \tag{1}$$

$$\text{2Tc}^{+6}\text{Tc}^{+4} + \text{2Tc}^{+7} \tag{2}$$

The coordination number of the technetium during complex formation can be changed between 4 and 9.

#### **6. Reducing agents and reduction of 99mTcO4** �

Technetium generated by Moly generator presents in the form of sodiumpertechnetate (99mTc-NaTcO4). In this pertechnetate ion, the oxidation state of technetium is +7 and structure of the 99mTcO4 � is pyramid tetrahedron in which Tc atom is present in the center of the tetrahedron with +7 oxidation state and four oxygen atoms located at the apexes of the triangular pyramid. This geometry and oxidation state is identical to the permanganate ion MnO4 � and perrhenate ion ReO4 � ion. Structure of the pertechnetate ion TcO4 � is shown in **Figure 2**.

Overall reaction

administrated in the concentration � <sup>10</sup>�<sup>9</sup> M.

*DOI: http://dx.doi.org/10.5772/intechopen.93449*

**7. Labeling of chelating agents with reduce technetium**

*Single-Photon Emission Computed Tomography (SPECT) Radiopharmaceuticals*

(diethylenetriamine pentaacetic acid) and gluceptate.

**8. Oxidation state of technetium for labeling**

in different oxidation states are as follows:

of technetium (pertechnetate 99mTcO�

**9**

299mTcO4 <sup>þ</sup> 16H<sup>þ</sup> <sup>þ</sup> 3Snþ2 99mTcþ<sup>4</sup> <sup>þ</sup> 8H2O <sup>þ</sup> 3Snþ<sup>4</sup> (5)

It is clear from the Eq. 4 that technetium reduces from higher oxidation state +7 to lower oxidation state +4. Under different chemical and physical conditions, other oxidation state of 99mTc such as 99mTc+3 and 99mTc+5 are likely to be formed or a mixture of all these oxidation states could possibly exist. Stannous chloride as a reducing agent is usually used in a very small amount while 99mTc is commonly

Technetium-99m after reduction forms reactive species and attains the ability to bind with a variety of chelating agents to generate the labeled product. In order to form the additive bond, normally, chelating agent donates the lone pairs of the electrons to make coordinate covalent bond with 99mTc. Compounds containing the electron donating group such as carboxylic group (dCOOH), amines (dNH2), hydroxyl (dOH), and thiol group (dSH) are good chelates such as DTPA

Technetium is found in variable oxidation states ranging from �1 to +7, but it frequently forms complexes in +5 oxidation state. A number of technetium complexes with other oxidation states also exist in increasing order [10]. Complex of technetium in +6, +2 and zero oxidation state are not synthesized because they are not fruitful for medical purpose. Different complexes of technetium that they from

• Complex of technetium in +7 oxidation state (Tc+7). Technetium naturally occurs in this state, and it is most stable and nonreactive toward any chelating agent in this oxidation state. Technetium in +7 oxidation state is found in the

• Complex of technetium in +5 oxidation state (Tc+5). Technetium is present in this oxidation state in the form of complexes such as99mTc-gluconate, 99mTcglucepetate, and 99mTc-citrate. During these complexes formation, reduction

oxidation state +5 is accomplished with stannous chloride in an aqueous medium. It is observed that technetium in +5 oxidation state have tendency to form the complex with sulfur containing molecules (dithiols) in solid state. In these sulfur complexes, four sulfur atoms are located at the corner of the square planes and oxygen atom at the apex of square pyramid. Compounds with six coordination number are preferably formed in the aqueous medium,

and molecules exhibit more stable structure in the form of octahedral geometry. Diaminodithiol (DATA) is one of the best examples of such compounds. In these complexes, oxidation state of technetium is +5 and

• Complex of technetium in +4 oxidation state (Tc+4). Oxidation state of technetium in complexes of TcO2 and hexahalo is +4. The reducing agent

complexes are neutral and stable in this oxidation state.

4) from +7 oxidation state to lower

form of technetium heptasulfide and pertechnetate 99mTcO4.

Pertechnetate 99mTcO4 is a nonreactive molecule and cannot be used directly for labeling; therefore, it is necessary to reduce the pertechnetate from +7 oxidation state to lower oxidation state for labeling purposes. For the reduction of the pertechnetate 99mTcO4 form +7 oxidation state to lower oxidation state, a variety of reducing agents are employed such as stannous citrate (C12H10O14Sn3), stannous tartrate (C4H4O6Sn), stannous chloride (SnCl2.2H2O), concentrated hydrochloric acid (HCl), dithionite (O4S2 �2 ), ferrous sulfate (FeSO4), and sodium boro tetrahdride (NaBH4). However, the most frequently used reducing agent in labeling of the compounds with technetium process is stannous chloride dihydrate (SnCl2.2H2O) [10]. Electrolysis can also be utilized as a method for reducing sodium-pertechnetate (99mTc-NaTcO4) and use zirconium as an anode and labeling compound. However, following common characteristics are being considered to choose a reducing agent in 99mTc chemistry.


Reduction of pertechnetate 99mTcO4 with the help of stannous chloride is accomplished in acidic medium, and reaction is given below.

$$\mathbf{3Sn}^{+2}\,\mathbf{3Sn}^{+4} + \mathbf{6}\,\mathbf{e} \tag{3}$$

$$\text{2}^{\text{99m}}\text{TcO}\_4 + \text{16H}^+ + \text{6e}^{\text{99m}}\text{Tc}^{+4} + \text{8H}\_2\text{O} \tag{4}$$

**Figure 2.** *Structure of pertechnetate ion 99mTcO4* �*.*

*Single-Photon Emission Computed Tomography (SPECT) Radiopharmaceuticals DOI: http://dx.doi.org/10.5772/intechopen.93449*

Overall reaction

technetium is +7 and structure of the 99mTcO4

choose a reducing agent in 99mTc chemistry.

acid (HCl), dithionite (O4S2

long time.

**Figure 2.**

**8**

*Structure of pertechnetate ion 99mTcO4*

ReO4

*Medical Isotopes*

oxidation state is identical to the permanganate ion MnO4

�2

� ion. Structure of the pertechnetate ion TcO4

atom is present in the center of the tetrahedron with +7 oxidation state and four oxygen atoms located at the apexes of the triangular pyramid. This geometry and

Pertechnetate 99mTcO4 is a nonreactive molecule and cannot be used directly for labeling; therefore, it is necessary to reduce the pertechnetate from +7 oxidation state to lower oxidation state for labeling purposes. For the reduction of the

pertechnetate 99mTcO4 form +7 oxidation state to lower oxidation state, a variety of reducing agents are employed such as stannous citrate (C12H10O14Sn3), stannous tartrate (C4H4O6Sn), stannous chloride (SnCl2.2H2O), concentrated hydrochloric

tetrahdride (NaBH4). However, the most frequently used reducing agent in labeling

of the compounds with technetium process is stannous chloride dihydrate (SnCl2.2H2O) [10]. Electrolysis can also be utilized as a method for reducing sodium-pertechnetate (99mTc-NaTcO4) and use zirconium as an anode and labeling compound. However, following common characteristics are being considered to

• It should give effectual reduction at compassionate pH environment.

• It should not incorporate within the final product of the complex.

• It should not interfere with complex formation procedure.

accomplished in acidic medium, and reaction is given below.

�*.*

• It should have long shelf life mean remain unaffected when they are stored for

• It should give well-defined oxidation state in order to generate intrinsic complex.

Reduction of pertechnetate 99mTcO4 with the help of stannous chloride is

), ferrous sulfate (FeSO4), and sodium boro

3Snþ<sup>2</sup> 3Snþ<sup>4</sup> <sup>þ</sup> 6 e (3)

<sup>2</sup>99mTcO4 <sup>þ</sup> 16H<sup>þ</sup> <sup>þ</sup> 6e99mTcþ<sup>4</sup> <sup>þ</sup> 8H2O (4)

� is pyramid tetrahedron in which Tc

� is shown in **Figure 2**.

� and perrhenate ion

$$\rm 2^{99m}TcO\_4 + 16H^+ + 3 \rm 8n^{+2.99m}Tc^{+4} + 8H\_2O + 3 \rm 8n^{+4} \tag{5}$$

It is clear from the Eq. 4 that technetium reduces from higher oxidation state +7 to lower oxidation state +4. Under different chemical and physical conditions, other oxidation state of 99mTc such as 99mTc+3 and 99mTc+5 are likely to be formed or a mixture of all these oxidation states could possibly exist. Stannous chloride as a reducing agent is usually used in a very small amount while 99mTc is commonly administrated in the concentration � <sup>10</sup>�<sup>9</sup> M.
