Materials and Methods

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DOWEX 50x8, seems difficult. But, the major used complexing agent for metals, DOTA, is not a specific ligand. Thus the presence of others metals requires higher quantities of DOTA for radiolabelling. In order to minimize the metallic impurities, D G A ® r e s i n which is specific to lanthanides and already used to purify scandium [16], w a s e m p l o y e d

This work aimed to produce and purify ^44mSc/⁴⁴Sc with high specific activities. Then the radiolabelling with DOTA was performed from scandium source in order to evaluate the specific activity with regards to all metallic impurities that could be present in the final source.

2. Materials and Methods

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made of 100 mg of ⁴⁴CaCO₃ pressed under 5000 tons to form a 10 mm diameter pellet. The obtained thickness was about 470 µm. To prevent the target contamination during irradiation, the target was placed between two 75 µm kapton foils.

On ARRONAX facility, ⁴⁴Sc was produced using an irradiation station named Nice3 devoted to the low activity productions (few mCi maximum). With this device, our target was placed in air, 6.6 cm away from a 75 µm Kapton foil ensuring the sealing at the end of beamline (Fig. 2). The targets were cooled by air during the irradiation.

2.3. Partition coefficients determinations

The distribution coefficient (KD ) quantifies the partition of an element between the aqueous solution and the solid phase and is defined as follows:

(1)

where Csolid is the concentration of elements sorbed onto the resin (in g/g of dry resin), and C_solution the total aqueous solution concentration of elements (in mol/L) which remains in solution after equilibration.

As the distribution coefficients were calculated as a function of dried resin mass, the percentage of humidity was determined by placing 5 samples of each pre-conditioned resin in oven at 105^◦C. Moreover as single and multi- elements standards are commercially available in dilute nitric acid and to avoid potential effects of nitrate ions on partition behaviour, aliquots standard solutions were transferred to a pre-cleaned with ultrapure HNO3 2% Teflon beaker and the solutions were evaporated to dryness. After complete evaporation, the solid residues were dissolved in HNO₃ or HCl and the process

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was repeated three times to ensure complete removal of initial anions. Then a mass of pre-conditioned DGA resin was dispersed in the studied aqueous solution. The suspensions were stirred for two hours that has been shown to be sufficient to reach equilibrium. The aqueous phases were collected by filtration and analysed. A blank solution (without resin) was prepared with each batch of equilibration experiment and analysed together with the samples, to determine the initial concentrations of each element. The acid solutions were collected and were diluted in HNO3 1% prior to analysis.

Measurements were performed on a Thermofischer ICAP 6500 DUO ICP- AES. Representative wavelengths for each element were selected with preference given to higher relative emissions and absence of interferences.

Knowing the initial (Cinit) and equilibrium (Ceq) aqueous concentrations of each element, Eq.1 can be rearranged as followed:

( )

(2)

where m (in g) is the weight of dried resin and V (in mL) is the total volume of aqueous solution. Equilibration experiments were replicated using freshly prepared multi-element standard solutions, and the final distribution coefficients were calculated based on the arithmetic averages of replicate analysis. The resin concentration (in g/mL) was chosen for each batch to minimize the global uncertainty of partition coefficient. The reproducibility of logarithm of KD was better than 5% for all elements.

2.4. Radiochemical separations

Firstly, the purification process was developed using an artificial target made from natural calcium (100 mg of natural carbonate calcium). A multi-

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element standard solution was prepared from single and multi-element standard solutions and then added to the artificial target after dissolution.

The obtained solution was loaded onto the DGA® resin (200 mg of pre- conditioned dried resin). The recovery of all elements as a function of acid type, concentration and elution volume was determined to define the elution profiles of all elements. The aim was to recover scandium selectively and quantitatively.

Then the purification process was applied to irradiated ⁴⁴CaCO3 targets. The targets were removed from the target holder and dropped into 4 mol.L⁻¹ HCl solution. The aqueous solution was loaded onto the DGA® column. At the end of the purification process, the scandium solution was evaporated to dryness and the, recovered in a small volume of HCl 0.1 mol.L⁻¹.

The final solutions were measured by a gamma-detector (ORTEC) with a high resolution HPGe detector to determine the radionucleidic purity and by ICP-AES to determine the concentration of potential major impurities.

enriched calcium recycling

As DGA resin is specific to lanthanides, a first solution with metals and calcium was recovered from purification process. It was evaporated to dryness and recovered in concentrated ultrapure hydrochloric acid (9 mol.L⁻¹). The solution was then loaded on an pre-conditioned AG1x8 column to retain all metallic impurities (Cu, Co, Fe...). The column was rinsed with 10 mL of HCl 9 mol.L⁻¹ to recover enriched ⁴⁴Ca. The eluted solution was evaporated to dryness and recovered in a mixture of bicarbonate buffer 0.1 mol.L⁻¹ (pH=10.33)/methanol. The solution was then filtered through 0.22 µm filters (Cellulose Acetate, Millipore) to discard supernatant and the residue was

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dried in a oven at 105^◦C to remove water and methanol. The obtained solid of calcium carbonate was suitable for manufacturing new targets.

Labeling DOTA with ^44m,44Sc

To 450 µL of solution of DOTA (i.e. 10 nmol, Macrocyclics Inc.) were added 50 µL (i.e. 2 nmol) of ⁴⁴Sc and mixed in a 2 mL screw-Cap Wheaton V- bottom vial. The solution was placed in a boiling water bath at 90^◦C for 30 min and then cooled till room temperature was reached. To test the radiolabelling yield, a radio-TLC was performed by spotting 2 µL onto a TLC Flex Plate (silica gel 60A, F-254, 200 µm, Selecto Scientific) and eluted with a developing solution of 0.04 mol.L⁻¹ aqueous NH4OAc/ Methanol, 50/50 (v/v). The activity distribution on the plates was assessed with a Packard Cyclone Phosphor-Plate imaging system (Perkin Elmer).