67GaZn separation with an organic adsorbent

Appl. Radiat. ht. Vol. 41, No. 6, pp. 575-578, ht. J. Radiar. Appl. Instrum. Part A

0883-2889190

1990

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Copyright 0 1990 Pergamon Press plc

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67Ga/Zn

Separation with an Organic Adsorbent

R. J. N. BRITS* ‘National

and

F. W. E. STRELOW

Accelerator Centre, PO Box 72, Faure 7131, South Africa and *Processing and Chemical Manufacturing Technology, CSIR, PO Box 395, Pretoria 0001, South Africa (Received 23 June 1989; in revised form 5 October 1989)

A “‘Ga/Zn separation method is presented which uses an organic polymer containing no ion exchange groups, instead of an ion exchange resin. With the apparatus described, high quality 67Ga citrate can be obtained in good yield with little effort. Values for distribution coefficients for Ga on various resins and at different HCI concentrations are presented

with 10 mL of the relevant solution containing a known amount of tracer 67Ga. Inactive Ga was only added when explicitly required. A preliminary investigation with 67Ga in 8 M HCl indicated that equilibrium is reached within 3 h. The phases were separated by filtration with a radiochemical filter and the 67Ga content of both the resin and liquid phase was measured by y-ray spectrometry. Care was taken to ensure that the two phases were measured under comparable conditions. The coefficients are presented in Tables 2, 3 and 4.

Introduction Gallium-67 with a half-life of 78.3 h and y-rays with energies of 93, 185 and 300 keV is a cyclotron-produced radioisotope for which a considerable demand exists. The isotope is usually supplied in citrate solution which is widely used in hospitals to detect malignant tumors and inflammatory lesions (Higashi et al., 1972). 67Ga is frequently produced through proton or deuteron bombardment of natural or enriched Zn targets (Helus and Maier-Borst, 1973). It is usually separated from Zn by ion exchange chromatography (Helus and Maier-Borst, 1973; van der Walt and Strelow, 1983) or by liquid extraction (Helus and Maier-Borst, 1973; Hupf and Beaver, 1970). An elegant separation can also be performed through extraction chromatography (Weinreich et al., 1982). Although other production routes for 67Ga are possible at the 200 MeV separated sector cyclotron at Faure, proton bombardment of Zn targets was chosen as the best option at present. It is desirable that a routine separation method should yield an acceptable product with a minimum of effort. Since we had experience with the ion exchange method of van der Walt and Strelow (1983) this method was further investigated. The results obtained and the separation method devised are reported in this paper.

Resin capacity

Solutions containing known concentrations of 67Ga were slowly pumped through Ga and known amounts of dried resin. The 67Ga activity was continuously monitored at the outlet of the column. Breakthrough curves were constructed and measurements of 67Ga on the resin and in the combined eluate at the end of each experiment confirmed the value obtained from the inflection point of the symmetrical breakthrough curves. The XAD-7 resin (Amberlite XAD-7, Rohm and Haas, also available from BioRad laboratories) was dried to constant weight in a vacuum distilling apparatus, sieved, and a fraction < 300 pm diameter was used in all subsequent work. For the breakthrough curve of this resin the gallium solution was pumped through 100 mg resin in a column with an i.d. of 6 mm at a flow rate of 0.2 mL/min.

Experimental Distribution

coeficients Separation

Approximate distribution coefficients were obtained by shaking overnight 100 mg of the dried resin *Author for correspondence (present address: Nuclear Safety, P.O.B. 7106, Hennopsmeer Africa).

procedure

and apparatus

The Zn target disc (2.7 g) was pressed from Zn powder (Goodfellow, Cambridge 99.9 + %) using steel dies. The separation apparatus is shown in Fig. 1. The bombarded Zn target was dissolved in concentrated HCI containing 500 pg Ti3+ to yield a

Council for 0046, South

575

R. J. N. BRITS and F. W. E. STRELOW

Fig. I. The separation apparatus. Zn is dissolved in beaker A with HCI from the reservoir. The solution is pumped through the resin in column C with peristaltic pump D. The column is washed and eluted with the solutions in B. The eluate runs to waste W, or to the evaporator E. V is connected to a vacuum pump. E is heated with coiled resistance wire. Solutions F are successively run into E and 67Ga is transferred to the sample vial with peristaltic pump G.

solution containing 1.4M &Cl, and 7M HCI. Slow suction on the dissolution vessel prevented the escape of acid vapours. The column (i.d. 6mm) contained 300mg XAD-7 resin with 7M HCI. A peristaltic pump fitted with silicon rubber tubing was used to pump the solution through the column at a flow rate of about 0.5 mL/min. Although silicon rubber is not an ideal material for this application, other rubbers tested adsorbed about 10% of the gallium activity during trial runs with tracer 67Ga, and therefore seemed to be even less suitable. The silicon rubber tubing had to be replaced occasionally. The resin containing the adsorbed 67Ga was washed with 12 mL of 7M HCI to remove residual Zn and traces of Ti. Finally ‘j7Ga was eluted with 12 mL of 0.5M HCI and this solution was evaporated. Acid vapours were removed by suction using an all-Teflon vacuum pump which was connected through a water-cooled condensor (Fig. 1). Nitric acid was added before the solution had been completely evaporated, to convert GaCl, to the less volatile nitrate and destroy any traces of organic material present. The supply tubing was rinsed with water which also was evaporated. The 67Ga salts remaining were dissolved in 10mL O.lM citrate solution and transferred to a sealed sample vial for further processing. The behaviour of Zn during the separation procedure was followed with 6sZn tracer. Fe and Ti were determined by atomic absorption using a Varian AA6 instrument with a carbon rod attachment.

the numerical value of the distribution coefficients of gallium with the XAD-7 and XAD-8 polymers in 7 M HCl. It shows that the values of the coefficients decrease with increasing concentration of zinc and that at larger zinc concentrations XAD-8 absorbs gallium more strongly than does XAD-7. Initially XAD-8 was selected for further investigations, but serious tailing of 67Ga during elution with 0.05 M HCI, made XAD-7, which did not show so much tailing, more attractive. Published elution curves (van der Walt and Strelow, 1983; Paradellis et al., 1984) using a BioRad AGSOW-X4 cation exchange resin and milligram quantities of gallium do not show any significant tailing. However, tailing on the BioRad resin, which was used by us in the past for the separation of nanogram amounts of 67Ga encountered in practice, required the use of relatively large elution volumes for complete recovery. Elution from XAD-8 with 0.1 or 0.5 M HCI, dilute HNO, or acetic acid did not lead to any reduction of tailing. Consequently XAD-7 was selected for further work. Distribution coefficients of gallium as a function of HCI concentration are shown in Fig. 2 for XAD-4, a polystyrene resin, and XAD-7 the acrylic ester resin, selected for this work. Neither resin contains ion exchange groups. The distribution coefficient curves resemble those published by Kraus et al. (1954) for an anion exchange resin. They also resemble distribution coefficients for the solvent extraction of gallium chloride complexes (HGaCI,) as pointed out by Kraus et al. (1954). Ion exchange and solvent extrac-

Results and Discussion The practical capacities of a number of resins for Ga at various concentrations of HCl as obtained by the flow-through experiments are listed in Table 1. Because no information on distribution coefficients of gallium in HCI seems to be available for polymer materials containing no exchange groups, such information is presented in Table 2, while Table 3 demonstrates the influence of the concentration of zinc on

Table I. Flow-through capacities of some dry resins for Ga in HCI Resin

BioRad AG 5OW-X4 BioRad AG I-X8 BioRad AG 5OW-X4 Amberlite XAD-4 Amberlite XAD-7

[HCtl

Capacity (mm01 g- ‘)

IM 6M 9M 9M 7M

0.69 2.8 0.057 0.0021 0.43

67Ga/Zn separation Table 2. Distribution coefficients for Ga with various Amberlite polymeric adsorbents in 2 and 8 M HCI Resin

2M HCI

XAD-I XAD-2 XAD-4 XAD-1 XAD-8

8M HCI

6.8 15 16 20 17

8.8 16 280 1.2 x 104 3.0 x I04

tion of Ga in HCl are thus to a large extent determined by the complex formation process. Because XAD-4 and XAD-7 do not contain ion exchange groups it seems reasonable to assume that interaction of HGaCI, with the organic skeleton of the resin occurs in some way, and that a process somewhat similar to solvent extraction occurs, the HGaCl,, at high HCl concentrations, preferring the inside of the resin particles for thermodynamic reasons. Titze and Samuelson (1962) concluded that Fe’+ in strong HCl was extracted by the aromatic structure of the resin that he used, and not by the ion exchange groups. The variation of the distribution coefficients of gallium with the amount of gallium present in 7 M HCl is shown in Table 4. Comparative coefficients for BioRad AG50W-X4 cation exchange resin in 8 M HCl (van der Walt and Strelow, 1983) are included. The coefficients for the cation exchange resin decrease much faster with increasing amounts of gallium than predicted by the application of mass action equilibria equations to the ion exchange process, even for amounts of gallium far below the capacity of the resin. This apparently indicates that an ion exchange process is not responsible for the uptake of gallium. An extraction-like uptake of gallium chloride (probably as HGaCI,) by the hydrophobic resin matrix may take place, but it is probably somewhat suppressed by the presence of the ion exchange groups, leading to distribution coefficients which are considerably lower than the distribution coefficients for XAD-7. The existence of Ga,CI, molecules in solution, which has been demonstrated by Raman spectroscopy (Sheka et al., 1966) can also play a role in the equilibria. The 67Ga/Zn separation is performed in a hot cell with the apparatus shown in Fig. 1. Elements that extract well as chloride complexes (Morrison and Freiser, 1957) may contaminate the 67Ga product. Iron(II1) was the only element identified as a possible contaminant. Iron is present in the zinc target disc at a level of about 20 ppm and traces are probably

577

Table 4. Variation

of distribution coefficients of Ga

GE3 (mmol/g resin)

D for XAD-7

-0.ooo 0.0067 0.017 0.034 0.067 0.12 0.13 0.24 0.36

13,oOa 9300 6600 2500 1100 440 4c!J.l 180 II0

of Ga with amount

Ga (mmol/g resin)

D for AG 5ow-x4

0.004 0.008 0.02 0.08 0.2 0.4

580 472 312 117 66 37

also present in the HCl. Experimentally it was found that iron(II1) closely follows gallium through the separation. The presence of titanium(II1) in the zinc solution ensures that iron, reduced to iron(I1) during the dissolution of zinc, is not reoxidized to iron(II1) during the adsorption process. Titanium is eluted by the first 3 mL of the 7 M HCl solution, but tailing of the large amount of zinc required a larger elution volume. 67Ga/Zn separations with known amounts of tracer 67Ga in the separation apparatus gave recoveries of about 92% with about 1Opg of iron and 1OOpg of zinc contaminating the 10 mL of 67Ga citrate solution. No discolouration of the resin, indicating radiation degradation, was observed during production runs. 67Ga losses occur mainly during the evaporation and transfer steps.

10:

?o’

lo?

D

IO’

10’

Table 3. Distributmn coefficients for Ga on XAD-7 and XAD-8 in 7 M HCI at various Zn concentrations

1zn1 0 0.45 M 0.90 M 1.35 M

D

for XAD-7 1.3x104 1.9 x IO’ 5.0 x IO’ 3.5 x IO’

1zn1 0 0.76 M 1.5 M 3.0 M

D

for XAD-8 I x 8x 6x 3x

IO’ IO’ IO’ IO’

IO’

2

4

6

B

10

CHCU,M Fig. 2. D as function of HCI concentration for (A) XAD-4 and (B) XAD-7.

R. J. N. BRITS and F. W. E. STRELOW

578

of carrier-free

Conclusion A rapid 67Ga/Zn separation method has been developed. In respect of simplicity, yield and product quality it compares favourably with other published methods. The possibility of using solid polymer adsorbents instead of ion exchange resins may also be of interest in other cases, e.g. a “‘In/Cd separation in 4M HBr.

References Helus F. and Maier-Borst W. (1973) A comparative investi-

gation of methods used to produce 67Ga with a cyclotron. In Radiopharmaceuticals and Labelled Compounds, p. 3 17, IAEA/SM/171/21. IAEA, Vienna. Higashi T., Nahayama Y., Murata A., Nakamura K., Sugiyama M., Kawaguchi T. and Suzuki S. (1972) Clinical evaluation of “‘Ga-citrate scanning. J. Nucl. Med. 13, 196.

Hupf

H. B. and Beaver J. E. (1970) Cyclotron

Gallium-67.

Int. J. Appl. Radiar. Isot. 21,

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production

Kraus K. A., Nelson F. and Smith G. W. (1954) Adsorbability of metals in hydrochloric acid solutions. J. Phys. Chem. 58, 1 I, Morrison G. H. and Freiser H. (1957) Solvent Exfraction in Analytical Chemistry, p. 129. John Wiley, New York. Paradellis T., Vourvopoulos G. and Paleodimopoulos E. (I 984) The production of “‘Ga with a tandem accelerator. J Radioanal.

Nucl.

Chem.

Art. 84, 263.

I. S. and Mityureva T. T. (1966) The Chemisrry ofGallium, pp. 73-75. Elsevier, Amsterdam. Titze H. and Samuelson 0. (1962) uber die Sorption von Eisen (III) an Kationaustauschern aus Salzgure. Acta. Sheka

I. S.. Chaus

Chem.

&and.

16, 678.

Walt T. N. van der and Strelow F. W. E. (1983) Quantitative separation of Gallium from other elements by cationexchange chromatography. Anal. Chem. 55, 212. Weinreich R., Chamma D. F. S., De Costa e Silva A., Fernandes L. and Braghirolli A. M. S. (1982) Extraction chromatography in isotope production: application in the production of 67Ga and “‘Tl. J Labelled Compd. Radiopharm.

19, 1423.