PROCESS FOR THE PRODUCTION OF GALLIUM RADIONUCLIDES

Abstract

The invention provides a process for the production of gallium radionuclides, comprising irradiating a ceramic zinc phosphate target with a proton beam.

Claims

1. A process for the production of gallium radionuclides, comprising irradiating a ceramic zinc phosphate target with a proton beam.

2. The process of claim 1, wherein the proton beam is provided by a particle accelerator.

3. The process of claim 1, wherein the ceramic zinc phosphate target has the formula Zn.sub.3(PO.sub.4).sub.2.xH.sub.2O, wherein x is an integer in the range 0 to 4.

4. The process of claim 1, wherein the ceramic zinc phosphate target comprises zinc in the form of .sup.natZn.

5. The process of claim 1, wherein the ceramic zinc phosphate target comprises zinc enriched in .sup.68Zn, .sup.67Zn, or .sup.66Zn.

6. The process of claim 1, wherein the ceramic zinc phosphate target comprises zinc that is >99% .sup.68Zn.

7. The process of claim 1, wherein the ceramic zinc phosphate target has a density in the range 0.1 to 4 g/cm.sup.3.

8. The process of claim 1, wherein the proton beam has an energy level in the range 4 MeV to 30 MeV.

9. The process of claim 1, wherein the proton beam has an intensity in the range 10 to 1000 μA.

10. The process of claim 1, comprising the steps: providing a plate having a recessed portion, wherein the recessed portion has a surface of ceramic or metal; placing the ceramic zinc phosphate target in the recessed portion; covering the ceramic zinc phosphate target with a foil such that the ceramic zinc phosphate target is encapsulated by the foil and the surface of the recessed portion, securing the foil to the plate such that the ceramic zinc phosphate target is fixed relative to the plate; wherein the foil has a higher melting temperature than ceramic zinc phosphate target; and irradiating the encapsulated ceramic zinc phosphate target with the proton beam.

11. The process as claimed in claim 10, wherein the foil is a cobalt-containing foil.

12. (canceled)

13. (canceled)

14. A process for the production of gallium radionuclides, comprising irradiating a ceramic zinc target with a proton beam, wherein said ceramic zinc target is produced by an acid base reaction between zinc oxide and an inorganic or organic acid.

15. The process as claimed in claim 14, wherein the ceramic zinc target is selected from the group consisting of zinc sulfate, zinc sulfide, zinc carbonate, zinc acetate, zinc propionate, zinc trimethylacetate and mixtures thereof.

16. The process of claim 3, wherein the zinc is in the form of .sup.natZn.

17. The process of claim 3, wherein the zinc is enriched in .sup.68Zn, .sup.67Zn, or .sup.66Zn.

18. The process of claim 3, wherein the zinc is >99% .sup.68Zn.

19. The process of claim 1, wherein the ceramic zinc phosphate target has a density in the range 1.5 to 3 g/cm.sup.3.

20. The process of claim 1, wherein the proton beam has an energy level in the range 10 MeV to 16 MeV.

21. The process of claim 1, wherein the proton beam has an intensity in the range 50 to 300 μA.

Description

[0068] The invention will now be described with reference to the following non limiting examples and figures.

[0069] FIG. 1: Weight percentages of elements in zinc phosphate target

[0070] FIG. 2: Isotope distribution in natural zinc

[0071] FIG. 3: Plan view of a cover having an aperture in one embodiment of the invention

[0072] FIG. 4: Plan view of a plate having a recessed portion in one embodiment of the invention

[0073] FIG. 5: Side view of the cover of FIG. 3

[0074] FIG. 6: Side view of the plate of FIG. 4

[0075] FIG. 7: Piece of target material and a piece of foil

[0076] FIG. 8: Side view and enlarged side view of the apparatus formed from the cover, plate, target nuclide, and foil in one embodiment of the invention

[0077] FIG. 9: Exploded view of the apparatus formed from the cover, sealing rings, plate, foil, and target nuclide in one embodiment of the invention

[0078] FIG. 10: The ceramic zinc target (mid) is shown between the bottom (left) and top (right) of the target holder

[0079] FIG. 11: Production rate with targets of different mass area

[0080] FIG. 12: Image showing surface marks after beam impact with 16 MeV protons on a target foil. The superimposed thread net with mm resolution indicates area of impact.

EXAMPLES

[0081] Proton Beam

[0082] The proton beam was produced by a Cyclotron Scanditronix MC-35 instrument. The target station, where the target holder is clamped, is a custom made device made to fix target holders with dimensions 42×40×3 mm. The target surface is held perpendicular to the beam entrance tube. The backing of the target holder is cooled by a constant flow of water.

[0083] Dose Calibrator

[0084] Activity measurements were carried out on a Capintec CRC 55 tW dose calibrator.

[0085] For testing of target physical properties and radioisotope production parameters targets have been made from natural zinc (.sup.natZn).

[0086] Preparation of Target Material

[0087] Target material was prepared by mixing zinc oxide (ZnO) with dilute phosphorous acid (H.sub.3PO.sub.4). The resulting cement, consisting of Zn.sub.3(PO.sub.4).sub.2.4H.sub.2O, is shaped by molding it to compact ceramic discs, or coins, before its spontaneous solidification. The molded coin dimensions are 17 mm in diameter with variable thickness, typically between 0.2-2.0 mm, in order to fit within the target holder. The crystal water is eliminated from the ceramic coin by baking at high temperature for dehydration. The resulting dehydrated ceramic target (FIG. 10) consists basically of zinc phosphate with the formula Zn.sub.3(PO.sub.4).sub.2.

[0088] The current molding process of targets allows for production of only one target at a time, because of the fast and irreversible solidifying process that occurs after mixing of the phosphoric acid and the zinc oxide.

[0089] If crystal water was remaining in the target, it would be released and result in an increase in gas pressure under the foil during irradiation. The dehydrating baking step (500-900° C.) of molded targets must have been essentially quantitative since the targets exposure to accelerated proton beams showed intact Havar foil after every exposure.

[0090] Nuclear Reactions with Ceramic Targets of .sup.natZn

[0091] Natural zinc contains five different isotopes. Thus, proton reactions on targets of .sup.natZn results in radiogallium isotopes with different half-lives. Here, the investigation of yield from proton-induced reactions was done by quantification of the longer half-life isotope .sup.66Ga after about one day after end-of-bombardment, when .sup.68Ga has decayed. All quantitative measurements were done by a dose-calibrator with a preset calibration value for .sup.66Ga.

[0092] Targets with thickness between 0.25 and 1.68 (70-289 mg/cm.sup.2) were exposed to 16 MeV protons with different focus area and currents between 2.1 and 2.58 μA.

TABLE-US-00001 TABLE 1 Production data from five radiation run on zinc phosphate targets. 1 2 3.1 3.2 3-tot 4 5 Weight, g 0.1611 0.238 0.262 0.378 0.641 0.516 0.657 Thickness, mm 0.25 0.7 0.52 0.93 1.45 1.24 1.68 Density, g/cm.sup.3 2.83 1.5 2.22 1.79 1.95 1.84 1.72 Mass area, mg/cm.sup.2 70.8 104.8 115.6 166.6 282.2 227.3 289.4 Current, μA 2.1 2.27 2.58 2.58 2.58 2.35 2.1 Time, min 10 10 10 10 10 10 10 Activity, MBq 11.7 20.5 29.4 22.6 52 43.2 40.3 Rate, MBq/μAh 33.4 54.2 68.8 52.6 121.2 110.6 115.4 Rate/mass area, 0.471 0.517 0.591 0.315 0.429 0.487 0.399 MBq/μAh/mg/cm.sup.2 Note: all measured activities are 35% lower than true values because of self-absorption of radiation in the detector. Run three comprises a target sandwich of two discs with 3.1 on top against the beam entrance.

[0093] The resulting amount of activity (Bq) is normalized with current (μA) and irradiation time (h) during bombardment to production rate (Bq/(μAh). Calculated values for all runs are plotted against the respective mass area (mg/cm.sup.2) in order to display the effect of different target densities (FIG. 11). The mass area is calculated from the target weight divided by the area of the circular target disk (2.27 cm.sup.2). The true mass of zinc in the target in natural zinc is 51% of the calculated value that is based on the total target weight.

[0094] FIG. 11 shows a linear increase of the production rate of .sup.66Ga up to about 150 mg/cm.sup.2 in mass area. The decrease in slope at higher values of target mass area indicates approximity to the expected thick target yield (between 200 and 300 mg/cm.sup.2 totally, or 100-200 mg/cm.sup.2 related to the zinc content) for the used proton energy. Thick target yield is a constant showing the smallest mass area for when maximum production rate is achieved.

[0095] Calculation of Production Rate for .sup.68Ga

[0096] At present, the highest measured production rate for .sup.66Ga with our preliminary natural zinc target is 163.6 MBq/μAh with a 282 mg/cm.sup.2 target (value is corrected for detector efficiency). With a natural zinc metal target, Engle et al. (2012) demonstrated that .sup.68Ga is produced 10 times more efficient than .sup.66Ga with 13 MeV protons. Extrapolating this to our target values for .sup.66Ga could give a production rate for .sup.68Ga with the natural zinc ceramic target of the invention of 1.636 GBq/μAh (163.6 MBq/μAh×10).

[0097] Cyclotron production of .sup.68Ga for clinical use requires isotope enriched [.sup.68Zn]zinc to avoid other gallium isotopes within the product. Based on the isotope % of .sup.68Zn in .sup.natZn (19.024%), it is calculated that a ceramic target of which the Zn is 100% .sup.68Zn will yield 8.61 GBq/μAh.sup.68Ga, 5.26 times more than that of a target with a natural ratio of the zinc isotopes.

[0098] Beam Intensity

[0099] The current maximum available beam current at the external target position have so far been approximately 2.6 μA. Literature data from production of .sup.68Ga by liquid targets now on marked have been limited to 40 μA, and a relatively low production rate, 192.5 MBq/μAh. A more realistic production setting for clinical scale production will be in the range 40-100 μA for a target such as the ceramic target with the much higher production rate of 8 GBq/μAh.

[0100] Experiments performed with a 2.3 μA beam (FIG. 12) of focused protons, enabled investigation of target material integrity toward high beam current. Our results with a 2.3 μA beam showed, with a 4 mm.sup.2 impact area, that the target could withstand a 57 times higher current if distributed evenly on the available 227 mm.sup.2 target area. Hence, results from these tolerance experiments shows target resistance with high currents in the range of 100 μA proton beam sufficient for production of 500-1000 GBq .sup.68Ga. This activity level allows for multi dose production and satellite center distribution.

[0101] Estimates from our preliminary results on the new target predict production rates of .sup.68Ga about 8 GBq/μAh which is higher than earlier reported metal targets, about 5 GBq/μAh.

[0102] The combination of our new invented target material, with the target holder, enables proton beams with proton currents necessary for large scale nuclide production, 500-1000 GBq .sup.68Ga.