Research of Potential Production ^94mTc in Medical Cyclotron

The essence of the experiment was to produce positron-emitting ^94mTc using the capabilities of a small radiochemical laboratory at the PET center. To achieve this, we faced 4 tasks:

a) Selection of the composition of a molybdenum solution for irradiation on a cyclotron;

b) Selection and programming of the target device;

c) Development of a method for purifying Tc from positron-emitting isotopes in an irradiated solution;

d) Definition of qualitative analysis of the obtained product for the technetium isotope composition.

- Preparation of liquid target solution

In this research, it is irradiated molybdenum of natural isotopic composition (Table 1).

As a target substance was used, an aqueous solution of potassium molybdate with a molybdenum concentration of about 100 mg/ml, was obtained by dissolving dry molybdenum (VI) oxide in 1М КОН.

- Cyclotron targets

Work on the production of technetium was carried out on the Siemens RDS-111 cyclotron. The target device is a modified standard TCU designed to produce radionuclide nitrogen-13. This allows the entire cycle of obtaining radionuclides to be carried out automatically. The operating principle of this device is shown schematically in Figure 2. The HPLC pump with a capacity of 1.5 ml/min feeds a solution of the target substance into the volume 3 ml aluminum target through a mechanical valve set to a system pressure of 300 PSI and the pump constantly supports it during irradiation. After irradiation, a remotely controlled valve opens and the pump flows over the target solution into a hot box in the laboratory.

- Purification of technetium isotopes from radionuclide impurities

The produced technetium is stabilized in the chemical form of an aqueous solution of pertechnetate. The main part of radionuclide impurities to technetium are positron-emitting radionuclides, which are obtained from water by reactions ¹⁸O(p;n)¹⁸F (Т_1/2=110 min) and ¹⁶O(p;α)¹³N (Т_1/2=10 min). For this research, the obtained solution is delayed until ¹³N is fully decayed for at least 2 hours. ¹⁸F is formed as fluoride anions and is removed from the solution by precipitation with CaF₂ as an isotopic carrier:

Ca²⁺ + ¹⁹F^- + ¹⁸F^- = Ca¹⁹F¹⁸F↓; (Ca²⁺ + TcO₄- ≠).

- Radioisotope measurements by γ-spectroscopy

A 100 µl sample with an activity of about 1 MBq was added to a 3 ml vial of water and mixed thoroughly. The radionuclide composition was assessed using a γ-spectrometer HPGe with detector GEM30, manufacturer ORTEC. Since positrons annihilate with the emission of γ-quantum with energy 511 keV, then along this line it is possible to identify positron emitters including ^94mTc, which does not have its own unique γ-line. As can be seen from Table 2, other isotopes of technetium have unique γ-energy lines. Shows itself especially well ^99mТc, having a single, separate from other isotopes γ-line 140,45 keV.

Isotopes technetium production

In the work, several irradiations with a current of 30 μA were performed from 5 to 30 minutes. The pressure in the target during irradiation was constantly maintained at 300 PSI. Nuclear reactions with molybdenum isotopes can generate the radionuclides, presented in Table 3.

Accordingly, if we use isotopically pure Mo, we will obtain the only isotope we need, for example, ^94mTc from ⁹⁴Mo. This will also ensure high yields of the target radionuclide from irradiation. The only difficulty is the high cost of isotopically pure molybdenum. And since the physical consumption of molybdenum for the production of technetium is very low, it is possible to regenerate molybdenum for its repeated irradiation.

Pertechnetate isolation

2 ml of 0.1 M NaF was pre-added to the vial prepared for collecting the target substance. After unloading the irradiated solution and mixing, 0.5 M CaCl² was added dropwise to the solution until a white precipitate completely formed. It was then passed through a sterilizing syringe nozzle with 0.22 µm pores, ¹⁸F together with precipitate was retained on the filter, and TcO₄^- passed into the filtrate. More effective ¹⁸F-fluoride removal is also possible, if the CaCl² solution is placed in advance, and the isotopic carrier NaF is added after unloading the target substance.

Results of γ-spectroscopy

After cleaning from ¹⁸F and a delay of more than 2 hours for decay of ¹³N, the samples were analyzed on an γ-spectrometer. Spectrum was obtained and deciphered in the form of a diagram in Figure 3. There is a clean line at 140 keV, belonging to the isotope ^99mТc, and line 511 кэВ, belonging to positron emitters. As well as lines belonging to other isotopes of technetium. It turns out that this method can be used for the production of ^99mTc from stable ¹⁰⁰Mo, which has a great advantage, compared to technetium from the generator, in the absence of the long-lived parent radionuclide ⁹⁹Mo [10].

Dynamic γ-spectroscopy by the line 511 keV

One of the samples was analyzed on an γ-spectrometer every 30 minutes. Based on the obtained data was done graphic representation of the decay rate of positron emitters in the sample (Figure 4). A comparative analysis was carried out with the decay rate of ^94mТc, taking the coinciding points at 30 and 60 minutes as the calculated activity. As can be seen from the graphic, the decay of the sample almost coincides with the decay of ^94mТc, this indirectly confirms that among positron emitters ^94mТc gives the largest share to the line 511 keV. Additionally, a graphic was done of the decay rate of ¹⁸F, taking as the calculated value activity the difference between «decay of positron-emitting r/n» and «decay of ^94mТc» in the last point of the graph. The decay rate of ¹³N is taken as the calculated value activity of the difference between decay graphics in the first point of the graph. As can be seen, these graphics are far from the main one, and therefore their content is at the of small impurities.

For further scientific work in this direction, it is necessary first of all refine the separation methodology pertechnetate anions not only from fluoride but also from ¹³N in anionic form. After which, to synthesize the radiopharmaceuticals, it will be necessary to construct a new or redesign already existing automated radiochemistry synthesizer. The synthesis itself is hypothetically ordinary – useful RPs, labeled with the isotope ^99mТc, and methods of their analysis are used everywhere. To obtain ^94mТc without other isotopes of technetium expensive isotopically pure ⁹⁴Mo is required. And the main problem is allocation with minimal losses of molybdenum from irradiated solution. Without this, the research direction will not be economically justified.

This paper demonstrates the possibility of obtaining various technetium isotopes in a liquid target device of a low-energy proton accelerator. Particular attention should be paid to the positron-emitting isotope ^94mTc. The optimal half-life of 52 minutes allows chemistry reactions with ^94mTc to obtain radiopharmaceuticals in PET diagnostics. In the future, if the irradiation parameters are optimized and isotopically pure ⁹⁴Mo is used in the target substance, it will be possible to obtain high yields of the target radionuclide.

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