**3.1 Reactivity**

Reactivity is a concept used for many things in chemistry [20, 21]. In this paper, the focus will be if a determined reaction can occur or not, or if a "secondary" reaction can take place instead of the expected one.

Reactivity encompasses both thermodynamic factors and kinetic factors. For example, it is commonly stated that the reactivity of alkali metals (group one metals) (Na, K, etc.) increases down the group in the periodic table [20, 21]. The behavior is shown in the periodic table in **Figure 3**.

Reactivity is related to the rate at which a chemical substance tends to undergo a chemical reaction in time. In pure compounds, reactivity is regulated by the physical properties of the sample. For instance, grinding a sample to a higher specific surface area increases its reactivity. In impure compounds, the reactivity is affected by the inclusion of contaminants [22].

In double-replacement reaction (most common in the fabrication of medical radioactive sources), if one of the products isn't aqueous, by rule of thumb the reaction is possible [22].

**Figure 3.** *Reactivity shown in the periodic table.*

*Radiopharmaceuticals - Current Research for Better Diagnosis and Therapy*

$$AB + CD \to AD + CB\tag{4}$$

In this reaction, A and C are positively-charged cations, while B and D are negatively-charged anions. Double-replacement reactions generally occur between substances in aqueous solution. In order for a reaction to occur, one of the products is usually a solid precipitate, a gas, or a molecular compound such as water [19].

For example, the 1982 patent (US Pat. n. 4.323.055), filed by the Minnesota Mining and Manufacturing Company [23], describes a method of impregnating Ag rods with iodine-125, forming the core of a brachytherapy seed. The silver rods previously reacted to for a layer of silver nitrate. That modified rod reacted with the radioactive NaI<sup>125</sup> solution. The reaction will be:

$$\rm AgNO\_3 + NaI^{125} \to AgI^{125} + NaNO\_3 \tag{5}$$

Accordingly with **Table 1** (explained ahead):

$$\text{AgNO}\_{3\ (aq)} + \text{NaI}^{125}|\_{\text{(aq)}} \to \text{AgI}^{125}|\_{\text{(s)}} + \text{NaNO}\_{3\ (aq)}\tag{6}$$

Because there is a solid product, theoretically the reaction will occur.

For example, if the silver rod wasn't pure silver and had contained potassium in high proportions, KI125 will form more favorably than AgI<sup>125</sup> because potassium is more reactive than sodium.

#### **3.2 Electronegativity**

Electronegativity is a measure of the tendency of an atom to attract a bonding pair of electrons. Large electronegativity values indicate a stronger attraction for electrons than small values. Electronegativities increase from left to right across the periodic table (**Figure 4**). Elements on the left of the periodic table have low electronegativities and are frequently called electropositive elements [24].

If an atom B is more electron negative than A, the electron pair is dragged right over to B's end of the bond (Eq. (7)). A has lost control of its electron, and B has


#### **Table 1.**

*Solubility guidelines for Aqueous Solutions.*

*Start Here When Performing Radiochemical Reactions DOI: http://dx.doi.org/10.5772/intechopen.98766*

**Figure 4.** *Electronegativity shown in the periodic table.*

complete control over both electrons, forming an ion pair [25]. Electronegativity series follow **Figure 4**.

$$\mathcal{A}^+ \xrightarrow[\circ]{\bullet} \mathcal{B}^+ \tag{7}$$

When a situation with two possible outcomes is present, it is interesting to evaluate electronegativity. For example, the paper by Lee et al. [26] mixes pretreated silver rods with iodine-125, forming the core of a brachytherapy seed. Usually the radioactive iodine-125 solution is in the form of NaI125. Let's suppose that there is excess of Cl� as a contaminant in the mixture. **Figure 5** explain the possible outcome.

#### **3.3 Gibbs free energy**

In chemistry, a spontaneous process is one that occurs without the addition of external energy. A spontaneous process may take place rapidly or slowly, because spontaneity is not related to kinetics or reaction rate. According to the second law of thermodynamics, any spontaneous process must increase the entropy in the universe [27, 28]. This can be expressed mathematically as follows:

$$
\Delta \mathbf{S}\_{universe} = \Delta \mathbf{S}\_{system} + \Delta \mathbf{S}\_{surroundings} > \mathbf{0} \tag{8}
$$

#### **Figure 5.**

*Scheme of what happens when two anions, Cl*� *and I*�*, with two different electronegativities compete for the same cation, Ag+ . AgCl will form in a higher rate than AgI. Since silver iodide is the desired product, the reaction yield is impaired.*

Measuring the entropy change in the universe is not practical and the real interest is to observe the desired system (chemical reaction). When a process occurs at constant temperature T and pressure P, the second law of thermodynamics can be rearranged and define a new quantity known as Gibbs free energy (**Figure 6**). In other words, Gibbs free energy is a thermodynamic potential used to calculate the maximum reversible work that may be performed by a thermodynamic system at a constant temperature and pressure. The Gibbs energy, G, represents also the thermodynamic potential that is minimized when a system reaches chemical equilibrium [27, 28].

The Gibbs free energy of a system at any moment in time is defined as the enthalpy of the system minus the product of the temperature times the entropy of the system [27, 28].

$$\text{Gibbs free energy} \to \text{G} = \text{H} - \text{TS} \tag{9}$$

The change in the Gibbs free energy of the system that occurs during a chemical reaction is therefore equal to:

$$
\Delta G = \Delta H - \Delta (T\text{S}) \tag{10}
$$

If temperature is constant:

$$
\Delta G = \Delta H - T\Delta S \tag{11}
$$

The change in the free energy of a system that occurs during a reaction can be measured under any set of conditions. If the data are collected under standard conditions, the result is the standard-state free energy of reaction (*Δ*G<sup>o</sup> ) [27, 28].

$$
\Delta G^0 = \Delta H^0 - T\Delta \mathcal{S}^0 \tag{12}
$$

*Start Here When Performing Radiochemical Reactions DOI: http://dx.doi.org/10.5772/intechopen.98766*


Reference [30] has a 25-page list of Gibbs Free Energy values.

Continuing to use the paper by Lee et al. [26] as an example, one of the methods is to pre-coat the silver rod with *PO*<sup>4</sup> �<sup>3</sup> forming *Ag*3*PO*<sup>4</sup> following:

$$\text{Ag}\_3\text{PO}\_{4\text{ (s)}} + \text{3NaI}^{125}|\_{\text{(aq)}} \to \text{3AgI}^{125}|\_{\text{(s)}} + \text{Na}\_3\text{PO}\_{4\text{(s)}}\tag{13}$$

#### **Figure 6.**

*Explanation of the Gibbs Free Energy equation indexes. \*activation energy is the minimum amount of energy that must be provided to compounds to result in a chemical reaction [27–29].*


Gibbs free energy for the equation is:

$$
\Delta \mathbf{G}^0 = \Delta \mathbf{G}^0\_{\text{products}} - \Delta \mathbf{G}^0\_{\text{reactants}} \tag{14}
$$

*<sup>Δ</sup>G***<sup>0</sup>** <sup>¼</sup> -2017.57+ 766.536 = �1251.034 kJ/mol.

*ΔG***<sup>0</sup>** < 0 = Favorable, or spontaneous reactions.

To correlate between 2 reactions, it is more practical to investigate activation energy. A reaction with lower activation energy will be preferable, thus preferable to occur. **Figure 7** explains it.

For example, for the AgI<sup>125</sup> source fabrication, ions such as Cl� and Br� might be present. Activation energies are for AgBr 0.34 eV, AgI 0.48 eV, and 0.53 eV for AgCl. In a reaction when Br- and I- are present, is more likely that AgBr will form more easily than AgI. And, in a reaction when Cl� and I� are present, is more likely that AgI125 will form more easily than AgCl. This contradicts the previous electronegativity statement. All of these influences are occurring at the same time, possibly influencing the final result [31–33].

#### **3.4 Solubility**

Solubility is the capability of a solid, liquid, or gaseous substance (named solute) to dissolve in solvent (usually a liquid) and form a solution. The solubility of a chemical is dependent on the solvent used, temperature, and pressure. Solubility does not depend on particle size (even large particles will eventually dissolve given enough time). It is measured by the concentration of the saturated solution. A saturated solution is a solution that contains the maximum amount of solute that is capable of being dissolved. In other words, adding additional solute no longer

**Figure 7.** *Two reactions with different activation energies.*

*Start Here When Performing Radiochemical Reactions DOI: http://dx.doi.org/10.5772/intechopen.98766*

**Figure 8.**

*Solubility. The degree of solubility ranges broadly depending on the substances, from infinitely soluble to poorly soluble (insoluble). Under certain conditions, the equilibrium solubility can be exceeded, yielding a supersaturated solution.*

increases the concentration of the solution. **Figure 8** explains solubility classifications.

To evaluate a desired reaction, **Table 1** can be used [22].

Solubility is important because is directly impacts the amount of radioisotope available for the reaction. It may affect distribution in the radiation source resulting in dosimetry issues. For example, in Benega et al. [34] a phosphorus-32 radioactive source for spinal cancer treatment was developed by mixing the radioisotope with a catalyst solution. This solution is then added to an epoxy resin. Both solutions need to result in a homogenous product. This won't be achievable if the isotope doesn't properly mix with the catalyst solution (water based).

The solubility product constant, Ksp, is the equilibrium constant for a solid substance dissolving in an aqueous solution. It represents the level at which a solute dissolve in solution. Eq. (16) shows the correlation.

$$a\mathbf{A}\_{(s)} \leftrightarrow b\mathbf{B}\_{(aq)} + c\mathbf{C}\_{(aq)} \tag{15}$$

$$K\_{sp} = \left[\mathbf{C}\right]^{\epsilon} \left[\mathbf{D}\right]^{d} \tag{16}$$

If two competing ions are present, solubility and quantity play an important role in each reaction will be preferable. For example, in the iodine-125 seed manufacture, NaOH is used in pH control. NaOH is soluble in water, resulting in ionic completion for the silver biding sites. It maybe would be better to use Fe(OH)3 that is insoluble. For instance, let's use the information in **Figure 2**. Iodine-125 solution has 50.3 GBq/mL and pH 10 (pOH 4). Calculating the amount of OH- and I-:

### **3.5 Characteristic of the isotope and other problems (pH, reaction volume, vial type)**

Characteristics of the isotope being used needs to be extensively investigated. Several problems may be present such as toxic decay atoms to a high possibility of contamination and volatilization. For example, Gold-198 used in colloid or nanoparticles for cancer treatment decays to the highly toxic mercury, demanding that a through toxicity study be done [35].

In another example, iodine salts and solutions are advised to be stored in dark bottles due to the fact that iodine reacts with light and undergo a photo decomposition reaction [36]. Even though performing a radioactive reaction in the absence of light is impractical, with this information the researcher can avoid light as much as possible.

In most cases, errors can be originated by unpredicted places. Eight different storage vials were tested by Kennedy et al. [37] in regards to its ability to contain iodine-131, used in thyroid cancer treatment, during 24 hours. Glass yielded the best results, with 10% loss and polyethylene the worse with >50% loss. He et al. [38] evaluate the iodine-125 activity intake on silver cores by varying the value of pH. They have found that the intake in the silver cores were higher at a low pH. The authors affirm that if pH is kept high, the Na125I solution will remain stable not releasing the 125I for silver binding. Both of these issues were confirmed by Daruich de Souza et al. [39].

Isotopes are being replaced for others or adapted in different fields all the time. For example, cobalt-60 teletherapy machines were the first developed. In the 1950's they were widely used, by producing a beam of gamma rays which was directed into the patient's body to kill tumor tissue. Cobalt-60 is produced by neutron irradiation of ordinary cobalt metal in a nuclear reactor. It is a high energy gamma ray emitter, 1.17 and 1.33 MeV, with specific activity of 44 TBq/g (≈1100 Ci/g). Because of its longer half-life, 5.27 years, cobalt-60 was widely used in radiation therapy. Nevertheless, this half-life still requires sources to be replaced every 5 years. As technology advanced, these machines were replaced by linear accelerators, that doesn't contain radiation sources [40, 41]. In recent years, the technology was revised, now in a new machine called gamma knife, were cobalt-60 sources are mounted [42]. Applications for Gamma Knife surgery include the treatment of cerebral vascular malformations, head tumors, certain pain conditions such as trigeminal neuralgia, along with the treatment of some movement and psychiatric disorders [42].

#### **4. Mock trials and radiation safety**

#### **4.1 How to set up mock trials**

The steps to set up mock trials are in **Figure 9**.

The first step is to analyze all possible reactions accordingly with item 3 of this chapter. After that, the reaction set up is investigated. Three important observations are:


*Start Here When Performing Radiochemical Reactions DOI: http://dx.doi.org/10.5772/intechopen.98766*

**Figure 9.** *Steps to set up mock trials [9, 43–45].*

3. Simplify set-up: less material usage result in less radioactive waste.

The third step is to follow the 3 radiation principles: distance, shielding, and time.


The fourth step is about setting up cold mock trials, meaning, the test of expected reaction and set-up with no radioactive material. Pay special attention to:


#### **Figure 10.**

*Attenuation Law and examples of shielding materials (apron and gloves from [46]).*


In Daruich de Souza PhD thesis [2] the set-up in **Figure 11** was used to handle iodine-125.

In Silva et al. [47] the cold fabrication of a phosphorous-32 radioactive source to be used in CNS cancer using epoxy resin was described. MCNP simulation was used to evaluate the radiation dose. Special attention was given to factors that can impact dose distribution such as source thickness and thickness variance. Two molds, Teflon and Silicon were used. The epoxy plaque fabricated with Teflon mold presented better agreement. MCNP for this plaque resulted in an average dose of 8.54 0.01% cGy/s. It was also found that, differences of less than 0.01 cm in thickness within the plaque lead to alterations of up to 25% in the dose rate. This work now set up the foundation to the hot tests.

It is also possible to access possible yields by using different equipment and procedure. In Uhm et al. [48] a nickel-63 betavoltaic battery using a threedimensional single trenched p-n transduction was designed. The optimum thickness *Start Here When Performing Radiochemical Reactions DOI: http://dx.doi.org/10.5772/intechopen.98766*

#### **Figure 11.**

*Set-up was used to handle iodine-125 [2].*

of the niquel-63 layer was determined to be approximately 2 μm, considering the minimum self-shielding effect of beta particles. The experiments to evaluate the P-N junction were first carried out by electron beam induced current technique employed to experimentally simulate beta emission from nickel-63 and to estimate the total device current. The open-circuit voltage was found to be 0.29 V and the short-circuit current was 3.3 A. The power output was found to be 66.5 W/cm<sup>2</sup> . From the e-beam test, the good operation of the P-N absorber was confirmed before a radioactive source was fabricated.

The fifth step is to use less radioactive material or a different radioisotope to practice. This will ensure that the expected reaction is working and that the radiation protection measuring methods are efficient. For example, the AgI<sup>125</sup> reaction can be performed by using AgI<sup>131</sup> initially. Iodine-131 has a half-life of 8.04 days (59.43 for iodine-125) with energy 364.49 keV gamma and 191.58 keV beta (29 keV average gamma for iodine-125). This has the advantage of:


But it has the disadvantages of:

• a higher gamma emission results in higher radiation exposure to the operator;

• one mCi (370 MBq) of each isotope result in a different number of atoms. The results obtained might not be representative of the real reaction:


#### **4.2 Radiation safety**

The guiding principle of radiation safety is "ALARA". ALARA stands for "as low as reasonably achievable". This principle means that even if it is a small dose, if receiving that dose has no direct benefit, it should be avoided. To achieve this:


The International Commission on Radiological Protection (ICRP) system of radiological protection is a fundamental outline for dealing with any exposure situation in a systematic and coherent manner. At its core, the system relies on the three principles of justification, optimization and dose limitation. The principle of justification ensures that any decision that alters the radiation exposure should do better than harm. The outcome needs to be beneficial to society and the environment. The principle of optimization is for application in situations for which the implementation of protection strategies has been justified. Optimization of the protection strategy ensures that the likelihood of incurring exposures, the numbers of people exposed and the magnitude of their individual doses should be kept as low as reasonably achievable, taking into account societal and economic factors. This means that the level of protection should be the best under the prevailing circumstances, maximizing benefit over harm. Reference levels are adopted as an indicator of the level of exposure considered tolerable. This guideline help liming the dose for workers and public (**Table 2**) [51–53]. Specific environmental discharge of radioisotopes can be found in Ref. [54].

The basic requirements for achieving the highest standard in radiation safety are:

