Nano-titania: a novel purification and concentration adsorbent for ¹²⁵I production for medical uses

Abstract

The presented work describes the efficient use of nano-crystalline titania (TiO₂) to remove trace levels of cesium radio-contaminants (¹³⁴Cs and ¹³⁷Cs) in iodine-125 (¹²⁵I) solution produced via neutron activation of natural ¹²⁴Xe target. The adsorption parameters of TiO₂ were investigated to attain the optimum purification and concentration conditions of ¹²⁵I solution. The maximum sorption capacity of Cs and ¹²⁵I were approximately 56 and 67 mg/g TiO₂, respectively. The final ¹²⁵I solution was of high radiochemical, radionuclidic and chemical purities, besides, it showed high radioactive concentration that confirming its suitability for nuclear medicine applications and ¹²⁵I brachytherapy sources preparation.

Graphical abstract

Introduction

¹²⁵I demand is increasing worldwide due to its suitability for research, therapeutic and diagnostic purposes [1,2,3]. It is used for all these purposes due to its unique physicochemical parameters such as: long physical half-life (59.4 days), 35 keV γ-rays, 27 keV X-rays and its high specific activity (No Carrier Added form) [4,5,6,7,8,9]. Moreover, It is one of the most interested radioisotopes suitable for brachytherapy applications for prostate cancer, breast cancer and brain tumor, beside its use in radioimmunoassay (RIA) procedures for the quantification of biomolecules concentrations (nanomole) such as hormones, drugs, etc. [1,2,3, 9, 10].

¹²⁵I is produced by the (n,γ) irradiation of natural or enriched ¹²⁴Xe target in nuclear reactor as show in Fig. 1. [11, 12]. The produced ¹²⁵I will undergo electron capture and decays to the stable ¹²⁵Te completing its radioactive decay process.

Fig. 1

Schematic diagram of ¹²⁵I production from ¹²⁴Xe target

In case of enriched ¹²⁴Xe gas production route, it is most favored due to the absence of any secondary nuclear reactions resulted in superior radionuclidic purity. But its main drawback is that enriched ¹²⁴Xe is a highly expensive target material. While in case of natural xenon gas production route, natural xenon is much cheaper than enriched ¹²⁴Xe, but natural xenon is containing a mixture of nine stable isotopes with percentages: ¹²⁴Xe (0.096%); ¹²⁶Xe (0.090%); ¹²⁸Xe (1.92%); ¹²⁹Xe (26.44%); ¹³⁰Xe (4.08%); ¹³¹Xe (21.18%); ¹³²Xe (26.89%); ¹³⁴Xe (10.44%); and ¹³⁶Xe (8.87%) [11, 13], which after neutron activation raises the level of radio-contaminants such as ¹³⁴Cs and ¹³⁷Cs contributing to the radionuclidic impurities of the produced ¹²⁵I as follows:

$$^{ 1 3 2} {\text{Xe }}\left( {{\text{n}},\gamma } \right){^{ 1 3 3} {\text{Xe}}}\mathop{\longrightarrow}\limits_{{\text{T}}_{ 1/ 2} = {5}.3 {\text{days}}}^{\delta \, = {\text{ 5 b }}\beta^{-}}\,^{ 1 3 3} {\text{Cs }}\left( {{\text{n}},\gamma } \right){^{ 1 3 4} {\text{Cs}}}$$

$$^{ 1 3 6} {\text{Xe }}\left( {{\text{n}},\gamma } \right){^{ 1 3 7} {\text{Xe}}}\mathop{\longrightarrow}\limits_{{\text{T}}_{ 1/ 2} = 0. 1 5 {\text{ min}}}^{{\delta \, = { 3}. 8 {\text{ b }}\beta^{ - } }}\,{^{ 1 3 7} {\text{Cs}}}$$

All of this necessitates the removal of ¹³⁴Cs and ¹³⁷Cs for the ¹²⁵I product when it is produced for the natural xeno gas, which is mainly accomplished via distillation [14]. Although the distillation is an effective technique, the need for high temperature operations (hundreds of degrees centigrade) is its main disadvantage.

For seeking an efficient sorbent to attain the efficient separation of ¹³⁴Cs and ¹³⁷Cs from ¹²⁵I, our attention was directed towards the use of nano-sorbents. Many scientific fields started to explore the effectiveness of nano-sorbents as novel replacements to the commonly used sorbents that are mainly as bulk materials [15]. As nano-sorbents interact with numerous ways with different ions in an aqueous solution based upon their nano-scale features such as size, shape, surface area and particle charge, this raises up the potentiality to achieve the required efficient separations capacity [16].

In this context, t-ZrO₂ use seemed to show new hypothesis as it provide the capability to control the adsorptive activity besides, its selectivity by changing the external solution pH [13]. The potential of t-ZrO₂ as an adsorbent for column chromatography separation, it was fully exploited its use fullness in a many of radiochemical separation and concentration procedures [15, 17, 18]. Also, nano-composite TiO₂/Poly(acrylamide-styrene sodium sulfonate) [TiO₂/P (AAm–SSS)] was used for Cs ions separation from its solution at pH 8, [19].

From all of that, the presented study discuss the effective use of nano-titania as a new adsorbent capable of purifying and concentrating ¹²⁵I that is produced via neutron irradiation of natural xenon gas.

Experimental

Materials

No-carrier-added sodium iodide (NCA Na ¹²⁵I, 3.7 GBq/mL in 0.1 N NaOH) was purchased from Institute of Isotopes, Budapest, Hungary. Radioactive ¹³⁷Cs was supplied by Eckert & Ziegler Company. Radioactive ¹³⁴Cs was produced via irradiation of CsCl target in Egyptian Second Thermal Research Reactor (ETRR-2).

Synthesis of nano-crystalline titania (TiO₂)

Nano-crystalline titania (TiO₂) was prepared as reported in [20, 21]. In brief, with ratio of 2:1 (v/v), titanium tetrachloride was added drop by drop to isopropyl alcohol. The formed mass, as semisolid, was left for 5 days. After that, it was IR dried using an infrared lamp at 80 °C for 2 days. The obtained solid material was heated for 2 h at 200 °C in a furnace. After drying, the obtained solid mass was grounded in a porcelain mortar then sieved to get particles size suitable for use in a chromatographic column. TiO₂ nanoparticles was formed with BET surface area and average pore diameter (Dp) 320 m² g⁻¹ and ~0.00,478 nm, respectively. The particles size was found to be ~40 nm [20, 21].

Batch sorption study

Determination of distribution coefficients of I⁻ and Cs⁺ ions on nano-crystalline (TiO₂)

Cs⁺ and I⁻ ions distribution coefficients (K_d) on TiO₂ matrix were determined at different pH values, using radioactive I⁻ and Cs⁺ tracers. In 50 mL stoppered glass vials, 20 mL solution containing radioactive I⁻ and Cs⁺ tracers was placed followed by suspending 200 mg of nano-titania sorbent, in each experimental. The mechanical shaker was used to shake these vials for 30 min at room temperature. The radioactivity of the solution was determined before and after equilibrium using Multichannel spectrometry coupled with a high purity germanium coaxial detector (USA) that was calibrated with: ¹⁵⁵Eu (86.5 and 105.3 keV), ⁵⁷Co(122.1 and 136.5 keV), ¹³⁷Cs (661.6 keV), ⁵⁴Mn(834.8 keV), and ⁶⁵Zn(1115.5 keV) as mixed source.

The distribution coefficients (K_d) were calculated using the following equation:

$$K_{\text{d}} = \frac{{\left( {A_{\text{i}} {-} \, A_{\text{r}} } \right)V}}{{A_{\text{r}} m}}{\text{Lg}}^{ - 1}$$

where A _i and A _r are the initial total radioactivity of 1 mL the solution and the un-adsorbed activity in 1 mL of the solution at equilibrium, respectively. V is the solution volume (mL) and m is the mass (g) of the sorbent. The standard deviation of K _d values was the mean of three experiments.

Determination of equilibrium time for the sorption of I⁻ and Cs⁺ onto nano-crystalline (TiO₂)

To study nano-TiO₂ kinetic performance, time dependence of sorption of I⁻ and Cs⁺ onto nano-TiO₂ was done by the determination of these ions distribution coefficient (K _d) at different intervals (5–30 min). The K _d of I⁻ was studied at pH 3, while that for Cs⁺ was studied at pH 12. The K _d values were evaluated as the mean of three consecutive experiments. The time that shows unchanged K _d represented the equilibrium indication.

Determination of zeta potential

Zeta potential was determined using PSS-NICOMP Zeta Potential/Particle Sizer 380ZLS (PSS-NICOMP, Santa Barbara, CA, USA). Zeta potential at different pH were measured, as a mean of 3 values, by mixing about 5 mg of the sorbent with 50 mL of deionized water and adjusting the pH of the solution using HClO₄ and NH₄OH.

Nano-TiO₂ column dynamic sorption studies

Determination of breakthrough profile of Cs⁺ ion and I⁻ from nano-TiO₂ column

In order to determine the Cs and I sorption capacity under dynamic conditions, two glass columns [8 cm (l) × 0.5 cm (i.d.)] having a glass wool piece in the bottom were packed with 0.5 g of TiO₂. On first nano-TiO₂ column, 50 mL CsCl solution (2.5 mg Cs mL⁻¹) at pH 12 (the pH adjusted using HClO₄ and NH₄OH) tagged with ¹³⁴Cs tracer (~36 MBq) was loaded with a flow rate of 0.5 mL min⁻¹. On second nano-TiO₂ column, 50 mL NaI solution (5 mg I/mL) at pH 4 and tagged with ¹²⁵I (~180 MBq) tracer was loaded with a flow rate of 0.5 mL min⁻¹.

Standard samples of feeding the ¹³⁴Cs and ¹²⁵I solutions, 2.0 mL, were kept as reference (C₀). The effluents, in fractions equal in volume to the reference (2.0 mL each), were collected. The ¹³⁴Cs and ¹²⁵I radioactivity in the reference (C₀) and effluent fractions (C) were evaluating by counting the 605 and 35 keV γ-ray energy peaks of ¹³⁴Cs and ¹²⁵I, respectively, using a HPGe detector. The ratio of count rate C of the effluent after equilibrium to the original feed ¹³⁴Cs solution was taken as the parameter to follow the sorption pattern.

The dynamic sorption capacity, Q, was calculated by the equation:

$$Q \, = \frac{{\left( {V_{ 50\% } \times C_{\text{o}} } \right)}}{W}\,{\text{M mole Cs or I}}/{\text{gm TiO}}_{ 2}$$

where, V _50% is the effluent volume (mL) at C/C _o = 0.5 (as indicated by measuring the counting rate of the initial solution and different effluent fractions), C _o is the initial concentration M⁻¹ of ¹³⁴Cs or ¹²⁵I and W is the column matrix weight.

Purification and concentration of ¹²⁵I solution from ¹³⁴Cs and ¹³⁷Cs radio-impurities

A 8 cm (l) × 0.5 cm (i.d.) chromatographic column with a glass wool piece in the bottom was packed with 1 g of nano-TiO₂ and conditioned at pH 12 using HClO₄ and NH₄OH. Simulation solution, as that produced from neutron irradiated of natural ¹²⁴Xe, was prepared by mixing 20 mL from ¹²⁵I (180 MBq) with radio-impurities ¹³⁴Cs (36 MBq) and ¹³⁷Cs (18 MBq). This simulation solution was adjusted at pH 12 and was loaded on the nano-TiO₂ column with flow rate of 0.5 mL min⁻¹. The effluent was collected and its activity was measured in an ionization chamber. The pH of purified ¹²⁵I was adjusted to 4 and it was concentrated by passing through 0.5 g of nano-TiO₂ [8 cm (l) × 0.5 cm (i.d.)] chromatographic column conditioned at pH 4 and with flow rate of 0.5 mL min⁻¹. The adsorbed ¹²⁵I was milked from the column using 0.5 M NaOH solution at flow rate of 0.5 mL min⁻¹. In order to estimate the elution profile, the eluate was collected as 0.5 mL and the each fraction activity was measured.

Quality control parameters of ¹²⁵I product solution

Elution efficiency

Passing 5 mL 0.5 M NaOH solution carried out elution of ¹²⁵I from chromatographic column. Fractions of eluted solution were collected in equal volume to the reference (0.5 mL each) with a flow rate of 0.5 mL/min. The elution efficiency was calculated by

$$E_{\text{eff}} ,\% \, = \frac{{I_{\text{E}} }}{{I_{\text{L}} }} \times 100$$

where, I _E is the activity of eluted ¹²⁵I as summations of collected elution fractions and I _L is the activity of ¹²⁵I loaded in column.

Radionuclidic purity

¹²⁵I eluate radionuclidic purity represents the proportion of ¹²⁵I radionuclide to the total eluate radioactivity that was evaluated using a γ-ray spectroscopy multichannel analyzer [22].

Radiochemical purity

¹²⁵I eluate radiochemical purity was determined using the ascending paper chromatography method by developing a Whatman No.1 paper strip by a mixture solution [75% methanol and 25% water (v/v)].

The R _f value was calculated using the following formula:

$$R_{\text{f}} = \frac{{{\text{The distance }}\left( {\text{cm}} \right){\text{ travelled by the I}}^{ - } {\text{radionuclide from the starting line to the peak position}}}}{{{\text{The distance }}\left( {\text{cm}} \right){\text{ travelled by the solvent from the starting line to the solvent front}}}}$$

Radiochemical purity, R _c, is the contribution of a specific isotope chemical species counts, n, to the total counts of the spot. It was calculated from the following equation:

$$R_{\text{c}} = \frac{{I_{\text{n}} }}{{I_{\text{t}} }} \times 100$$

where, I _n is counts of the specified radioisotope chemical form (cpm), determined by area under the corresponding R _f peak and I _t is the total counts in the spot applied to the start line of the chromatographic paper (cpm), under similar counting conditions.

Results and discussion

Production of ¹²⁵I

¹²⁵I is produced by neutron activation of natural or enriched ¹²⁴Xe gas as reported [9]. In this work, a simulation of producing ¹²⁵I from natural Xe gas was done by dissolving 300 mg NaI in 50 mL 0.1 N NaOH solution (5.0 mg I/mL) then adding 125 mg CsCl with stirring (2.5 mg Cs/mL) followed by tagging the whole mixture with 5.0 mCi ¹²⁵I, 1.0 mCi ¹³⁴Cs and 0.5 mCi ¹³⁷Cs radiotracers. The radioactivity of ¹²⁵I was measured in ionization chamber while ¹³⁴Cs and ¹³⁷Cs radiotracers were evaluated by γ-ray spectroscopy using multichannel analyzer, HPGe detector by monitoring the 605 and 661 keV peaks for ¹³⁴Cs and ¹³⁷Cs, respectively, Fig. 2.

Fig. 2

Typical gamma-ray spectra of ¹²⁵I solution containing ¹³⁴Cs and ¹³⁷Cs impurities

Batch sorption study

The K _d values of I⁻ and Cs⁺ ions at different time intervals are very efficient approach to evaluate the optimum nano-TiO₂ sorption contact time.

The plot of K _d versus time is demonstrated in Fig. 3. It is clear that by increasing the contact period of I⁻ and Cs⁺ ions with the sorbent, the K _d values increase and that a contact period of 10 min was enough to obtain the sorption equilibrium for I⁻ and Cs⁺ ions.

Fig. 3

Determination of the sorption equilibration time of I⁻ and Cs⁺ ions on TiO₂: K_d values for I⁻ and Cs⁺ ions were determined at pH 4 and 12, respectively

The adsorbed ions kinetics are controlled by many independent processes that can affect in series or in parallel, such as chemical reaction (chemisorption), external mass transfer (film diffusion), bulk diffusion and intraparticle diffusion. Due to the availability of reactive surface area of nano-TiO₂, it showed an extraordinarily fast rate of sorption. The nano-sorbent zeta potential is its surface charge and its determination clarifies the understanding the electrostatic interactions between the adsorbed ions and TiO₂. The two main parameters that intensively affect the zeta potential, and in turn the interactions between the adsorbed ions and adsorbent are pH and the ionic conditions [13, 14]. Besides, the pH change doesn’t only affect the adsorbed ions charges but also the adsorbent surface properties, showing a mutual effect that sharply needs to be considered for understanding their interactions. The results summarized in Table 1 show the zeta potential of TiO₂ at different pH values.

Table 1 Distribution coefficient (K _d) values of I⁻ and Cs⁺ TiO₂ ions at different pH and the zeta potential values of TiO₂ at the corresponding pH

In the pH range 1–4, the values of zeta potential value are positive. By increasing pH, the values of zeta potential pass through zero (isoelectric point at which the zeta potential is zero) then it goes to the negative increasing values up to pH 10. At pH 1–4, the sorbent zeta potential is a positive value showing no affinity for the positively charged Cs⁺ ion and adsorbs the negatively charged I⁻ ion. Also, at pH 3–4, the maximum I⁻ ion uptake was observed.

Under alkaline conditions, the negative zeta potentials indicated that the surface of nano-TiO₂ has a negative charge that adsorb efficiently the positively charged Cs⁺ ions onto negatively charged sites of nano-TiO₂ and confirming no affinity for the negatively charged I⁻ ions. The change in sorbent zeta potential with changing pH is confirming with the K _d values.

Nano-TiO₂ column dynamic sorption studies

Determination of breakthrough profile of Cs⁺ ion and I⁻ from nano-TiO₂ column

Figure 4 shows that the dynamic breakthrough profile of Cs at pH ~12 loaded on 0.5 g of prepared nano-TiO₂ matrix in glass column was found to be ~56 ± 2 mg Cs/g TiO₂. Ram et al. [13] showed that the breakthrough point was reached after 50 ± 2 mg of Cs was quantitatively retained by 1.0 g of t-ZrO₂ at pH 13.

Fig. 4

Breakthrough profile of ¹³⁴Cs on passing ¹³⁴Cs (2.0 mg Cs ml⁻¹) solution at pH 12 through a 0.5 g TiO₂ chromatographic column at a flow rate of 0.5 ml min⁻¹

Also, Fig. 5 shows that the dynamic breakthrough profile of ¹²⁵I at pH ~4 loaded on 0.5 g of prepared TiO₂ matrix in glass column was found to be ~67 ± 2 mg I/g TiO₂. It was reported that breakthrough capacity of t-ZrO2 for I⁻ ions is 30 ± 2 mg of I⁻ per gram of sorbent [23].

Fig. 5

Breakthrough profile of ¹²⁵I- iodide on passing ¹²⁵I (2.0 mg Cs ml⁻¹) solution at pH 4 through a 0.5 g TiO₂ chromatographic column at a flow rate of 0.5 ml min⁻¹

Purification and concentration of ¹²⁵I solution from ¹³⁴Cs and ¹³⁷Cs radio-impurities

In light of the ¹²⁵I radionuclide purity after the passage of ¹²⁵I solution containing ¹³⁴Cs and ¹³⁷Cs radio-contaminants, γ-ray spectrometric analysis of the separated ¹²⁵I samples was done. From Fig. 6, the absence of photo peaks pertaining to ¹³⁴Cs and ¹³⁷Cs confirms the success of the purification step by the quantitative removal of ¹³⁴Cs and ¹³⁷Cs. From the radioactivity data of ¹²⁵I measured before and after the purification step, it was observed that the radioactive yield of ¹²⁵I was ≥95%.

Fig. 6

Typical gamma-ray spectra of final ¹²⁵I product solution

Concentration of ¹²⁵I solution using nano-TiO₂ as adsorbent for the purified ¹²⁵I solution was done to improve the radionuclidic purity of ¹²⁵I solution. The breakthrough capacity of nano-TiO₂ for I⁻ ions was 67 ± 2 mg of I⁻ per gram of sorbent. The specific activity of ¹²⁵I was (1.3 × 10⁷Ci) per 1.0 g of iodine.

Quality control parameters of ¹²⁵I product solution

Elution efficiency

The elution yield was high and up to ~95%. Figure 7 shows elution profile of ¹²⁵I adsorbed on a column chromatography of nano-TiO₂ on passing 0.5 M NaOH solution at a flow rate of 0.5 mL/min.

Fig. 7

Elution profile of ¹²⁵I adsorbed on a column chromatography of nano-TiO₂ on passing 0.5 M NaOH solution at a flow rate of 0.5 ml/min

Radionuclidic purity

Radionuclidic purity of ¹²⁵I was found to be ~99.99%, Fig. 6, as no any other gamma-ray radio-contaminant energy peaks were detected in the ¹²⁵I eluate γ-ray spectra measured immediately after elution for 200 s [11, 13].

Radiochemical purity

Radiochemical purity expressed as % I⁻ anions in the ¹²⁵I elutes was evaluated by the paper chromatography method [11, 13]. Figure 8 shows that only one peak zone was detected on the radio-chromatogram of ¹²⁵I elutes at R _f value of 0.75 corresponding to I⁻ anions confirming radiochemical purity of ~98% I⁻.

Fig. 8

Radiochromatogram of ¹²⁵I eluted from TiO₂ chromatographic column

Statistical analysis

In this work, data were expressed as a mean ± SD. Statistical analysis was done using Minitab 16 where one-way analysis of variance (ANOVA). Differences were considered to be significant for values of P < 0.05.

Conclusion

Nano-crystalline titania (TiO₂) can be considered as a potential sorbent material for the separation of Cs radio-contaminants from ¹²⁵I solution that can be used for ¹²⁵I production form irradiated natural Xe gas, ¹²⁴Xe(n,γ)¹²⁵I. Nano- TiO₂ showed maximum sorption capacity of Cs and I ~56 ± 2 and 67 ± 2 mg/g TiO₂, respectively. The purified ¹²⁵I was easily concentrated also using TiO₂ column. The Purified ¹²⁵I showed high ¹²⁵I elution yield ~95% with high radionuclidic and radiochemical confirming its suitability for use in medical radio-diagnosis and radiotherapy.