Reduction of 68Ge activity containing liquid waste from 68Ga PET chemistry in nuclear medicine and radiopharmacy by solidification.

PET with 68Ga from the TiO2- or SnO2- based 68Ge/68Ga generators is of increasing interest for PET imaging in nuclear medicine. In general, radionuclidic purity (68Ge vs. 68Ga activity) of the eluate of these generators varies between 0.01 and 0.001%. Liquid waste containing low amounts of 68Ge activity is produced by eluting the 68Ge/68Ga generators and residues from PET chemistry. Since clearance level of 68Ge activity in waste may not exceed 10 Bq/g, as stated by European Directive 96/29/EURATOM, our purpose was to reduce 68Ge activity in solution from >10 kBq/g to <10 Bq/g; which implies the solution can be discarded as regular waste. Most efficient method to reduce the 68Ge activity is by sorption of TiO2 or Fe2O3 and subsequent centrifugation. The required 10 Bq per mL level of 68Ge activity in waste was reached by Fe2O3 logarithmically, whereas with TiO2 asymptotically. The procedure with Fe2O3 eliminates ≥90% of the 68Ge activity per treatment. Eventually, to simplify the processing a recirculation system was used to investigate 68Ge activity sorption on TiO2, Fe2O3 or Zeolite. Zeolite was introduced for its high sorption at low pH, therefore 68Ge activity containing waste could directly be used without further interventions. 68Ge activity containing liquid waste at different HCl concentrations (0.05-1.0 M HCl), was recirculated at 1 mL/min. With Zeolite in the recirculation system, 68Ge activity showed highest sorption.

Introduction

PET scintigraphy with 68Ga-labelled peptides is of increasing interest in PET imaging in nuclear medicine [1-8] and performed at >40 centres in Europe (current situation, 2010). In general, radionuclidic purity (RNP) of the eluate of these generators varies between 0.01 and 0.001% (68Ge vs. 68Ga activity). Liquid waste containing low amounts of 68Ge activity (further referred as 68Ge waste) is produced by eluting the 68Ge/68Ga generators and residues from PET chemistry. For several reasons in our facility, solid 68Ge containing waste (t½ = 9 months) is preferred over liquid waste. Since clearance level of 68Ge activity in waste may not exceed 10 Bq/g, as stated by European Directive 96/29/EURATOM, our aim was to reduce 68Ge activity in solution from >10 kBq/g to <10 Bq/g; which implies the solution can be discarded as regular waste. As an example: when a 1,110 MBq 68Ge/68Ga generator with a RNP of 0.005%, is eluted with 6 mL 1 M HCl, the eluate contains 55.5 kBq 68Ge activity. Eluting a 1,110 MBq 68Ge/68Ga generator three times a day, 200 days per year, and for 1 year will result in 33.3 MBq in 3.6 L (9.25 kBq/g). Although national legislation within the EU may vary per country, the rules may only be more strict. For example in our country, The Netherlands, legislation does not allow to store radioactive waste with half-lives of more than 100 days at local institutes for more than 2 years. After 2 years it is obligatory to store the here described waste in a special external waste facility, and at additional costs. In this facility waste is preferably compressed, therefore, liquid content is limited to <1% (v/w). The purpose of this study was to quantify 68Ge activity in our 68Ge liquid waste, and to concentrate and to transform 68Ge liquid waste to solid waste. In short: 68Geliquid ⇒ 68Gesolid, initially on a small scale. Liquid 68Ge waste was transformed to 68Ge solid waste by sorption of TiO2, Fe2O3 (325 and 500 mesh, respectively, Sigma-Aldrich, Zwijndrecht, The Netherlands) and Zeolite (Na2Al2Si3O10·2H2O, Zeolyst international, Conshohocken, PA, USA). Elution of 68Ge/Ga generator is performed with HCl, therefore 68Ge waste is acidic. Zeolite was investigated because high sorption at low pH could be achieved (manuscript Kamalika Roy submitted).

Experimental

68Ge-containing liquid waste

Fractionated elution of the generator revealed at the activity of 68Ge (eg. Bq per mL) was constant during elution, whereas the main 68Ga activity could be collected in a small volume (1 mL) [1]. Eluate from generators and left-over after ion-exchange prior radiolabelling is acidic and contain a certain amount of 68Ge activity [4, 8]. Quantification of 68Ge activity was performed in a well-type gamma counter as described earlier [1]. During 5 years of daily practice with 4TiO2- and 4SnO2-based 68Ge/68Ga generators (0.4–2 GBq per generator) the total amount of 68Ge activity was 160 MBq in 48 L.

TiO2 and Fe2O3 as sorbent

Sorption of 68Ge activity on variable amounts of TiO2 and Fe2O3 was investigated with 1 mL samples of 68Ge waste as f[pH] (pH range 1–10) and time (range 1–24 h). These results were used for further up scaling. Typical example: 150 mL of 68Ge waste was mixed with ±1.5 g of TiO2 or Fe2O3 and centrifuged at 200×g. One mL of supernatant was taken as a sample and 68Ge activity was quantified 24 h after sampling as described earlier [1].

Recirculation system

Eventually, to simplify the processing of 68Geliquid ⇒ 68Gesolid a recirculation system was used to investigate 68Ge activity sorption (see Fig. 1) on TiO2, Fe2O3 and Zeolite. Eluate of 68Ge/Ga generator is acidic, therefore Zeolite was also investigated because high sorption at low pH could be achieved (Kamalika Roy manuscript submitted). 68Ge waste at different HCl concentrations (0.05–1 M HCl), was recirculated at 1 mL/min and sorption of 68Ge activity on TiO2, Fe2O3 or Zeolite was monitored time-dependently. Recirculation system contained ±1 g of sorption material enclosed with cotton, glass fiber and filters of 35 and 0.45 μm.

Fig. 1

Recirculation system containing ±1 g of TiO2, Fe2O3 or Zeolite as sorption material enclosed with cotton, glass fiber and filters of 35 and 0.45 μm. 68Ge activity containing waste was recirculated at a flow rate of ±1 mL/min. Samples of the circulating liquid were taken at indicated time points (see also Figs. 5, 6)

Fig. 5

Sorption of 68Ge activity on Zeolite was investigated as f[pH]. After 24 h the samples were centrifuged. Supernatant was decanted and 68Ge activity was quantified. Sorption of 68Ge activity using Zeolite was optimal at pH <1

Fig. 6

Recirculation system with 68Ge waste in 1 M HCl. One gram of sorption material was enclosed, see Fig. 1. 68Ge activity was quantified at indicated time points. Zeolite showed optimal sorption of 68Ge activity within 4 h (>95%)

Results and discussion

Firstly, sorption on TiO2, Fe2O3 was investigated time-dependently. Sorption of 68Ge activity on TiO2 (0.5 g/50 mL 68Ge waste) was low (<20%) at pH <2 and high (>99%) at pH >6 (Fig. 2). Sorption of 68Ge activity on Fe2O3 (0.5 g/50 mL 68Ge waste), showed better result at pH 1–3 (>75% Fe2O3 and <25% TiO2) and increased also as f[pH] up to >99% at pH 8. Optimal sorption was obtained at pH ≥5 (Fig. 2). Secondly sorption on TiO2, Fe2O3 was investigated as f[mass] and additions of sorption material. Sorption of 68Ge activity increased after each addition of sorption material. Moreover, Fe2O3 surprisingly continues to lower the 68Ge activity logarithmically after each addition of Fe2O3, whereas with TiO2 the value of 10 Bq 68Ge per mL level was reached asymptotically. The procedure with Fe2O3 as sorption material reduces the 68Ge activity by approximately 90% after each addition of sorption material (Fig. 3), eg. from >10 kBq/g to <10 Bq/g in six procedures. Low amounts (10 mg/mL) of sorbent showed similar 68Ge activity sorption at later time points in comparison with an amount of 100 mg/mL (Fig. 4a, b).

Fig. 2

Sorption of 68Ge activity (10 kBq/g) on Fe2O3 or TiO2 was investigated as f[pH]. After 24 h the samples were centrifuged. Supernatant was decanted and 68Ge activity was quantified. Sorption of 68Ge activity using TiO2 or Fe2O3 was optimal at pH >8

Fig. 3

Samples of 68Ge/68Ga generator eluate (50 mL) were used to investigate 68Ge activity sorption on 0.5 g TiO2 or 0.5 g Fe2O3. pH of the eluate was controlled by addition of phosphate buffer, final pH was ~8, and gently vortexed. Twenty-four hours after each addition, the 50 mL was centrifuged and a sample of the supernatant was collected to quantify 68Ge activity

Fig. 4

Complexation of 68Ge activity of 68Ge containing liquid waste (pH 8) with Fe2O3 (a) or TiO2 (b) as sorbent as function of time (1–24 h) and mass of sorbent (10–100 mg/mL)

Zeolite was introduced since this has high sorption at low pH, therefore it was tested as f(pH) (Fig. 5). With Zeolite in the recirculation system (Fig. 1), 68Ge waste (0.05–1.0 M HCl) showed highest sorption (Figs. 6, 7). In our facility, eluate purification and concentration with anion chromatography with 5 M HCl is also applied [4]. The waste stream is thus very acidic, but Zeolite as sorption material showed similar results as with 1 M HCl (Fig. 7). Summarized, recirculation system, using Zeolite as sorbent, is more efficient, less time consuming and reduces 68Ge waste mass in comparison with TiO2 and Fe2O3 procedure. The overall 68Ge containing liquid waste was 160 MBq in 48 L and could be concentrated to 160 MBq in <1 kg solid waste.

Fig. 7

Since Zeolite showed an optimal sorption of 68Ge activity (Fig. 5), a column containing Zeolite (±1 g, Fig. 1) was tested with 68Ge waste in 0.05, 0.1 or 1.0 M HCl. 68Ge activity was quantified at indicated time points. Recirculation system using higher concentration of HCl showed high sorption of 68Ge activity at earlier time points

Conclusion

TiO2, Fe2O3 and Zeolite as sorbent, lower 68Ge-containing liquid waste down to 10 Bq/g. Recirculation procedure using Zeolite as sorbent is preferred since less intervention with 68Ge containing liquid waste has to be performed and solid waste mass is reduced.