Process for producing gallium-68 through the irradiation of a solution target

Abstract

The present invention relates to a process for purifying and concentrating 68 Ga isotope produced by the irradiation with an accelerated particle beam of a 68 Zn target in solution. The process according to the invention allows for the production of pure and concentrated 68 Ga isotope in hydrochloric acid solution. The present invention also relates to a disposable cassette suitable to perform the steps of purification and concentration of the process.

1 . A process for producing and purifying  68 Gallium radioisotope, the process comprising the following steps:
 irradiating a target containing a target solution including zinc using an accelerated particle beam;   diluting the irradiated target solution with water;   feeding the diluted target solution into a strong cation exchanger;   washing the strong cation exchanger;   eluting zinc isotopes from the strong cation exchanger with a zinc elution solution including acetone;   washing the strong cation exchanger;   eluting  68 Gallium isotope from the strong cation exchanger with hydrochloric acid solution to obtain an eluted solution;   feeding the eluted solution into a strong anion exchanger,   washing the strong anion exchanger; and   eluting  68 Gallium isotope from the strong anion exchanger with hydrochloric acid solution to obtain a final solution.   
     
     
         2 . The process according to  claim 1 , wherein the irradiated target solution is diluted at least 5 volume times with water. 
     
     
         3 . The process according to  claim 1 , further comprising the following step:
 complementing the eluted solution with another hydrochloric acid solution to obtain a complemented solution, wherein the complementing step is performed before feeding the eluted solution into the strong anion exchanger.   
     
     
         4 . The process according to  claim 3 , the complemented solution includes a molarity in hydrochloric acid between 7 M and 10 M. 
     
     
         5 . The process according to  claim 1 , wherein the accelerated particle beam is a proton beam produced by a cyclotron. 
     
     
         6 . The process according to  claim 1 , wherein the strong cation exchanger is preconditioned with water before feeding the diluted target solution into the strong cation exchanger. 
     
     
         7 . The process according to  claim 1 , wherein eluting zinc isotopes from the strong cation exchanger is performed with a solution of acetone 80%/HBr 0.5 M. 
     
     
         8 . The process according to  claim 1 , wherein the final solution includes  68 Gallium in a hydrochloric acid solution of molarity between 0.08 M and 1.2 M. 
     
     
         9 . The process according to  claim 1 , wherein the strong anion exchanger is preconditioned with hydrochloric acid solution before feeding the eluted solution into the strong anion exchanger. 
     
     
         10 . The process according to  claim 1 , wherein the target solution including zinc further includes a zinc salt diluted in nitric acid or hydrochloric acid, wherein the zinc salt is selected from the group consisting of zinc nitrate, zinc chloride, zinc chlorate, zinc bromide, zinc iodide or zinc sulfate. 
     
     
         11 . The process according to  claim 1  further comprising the following steps:
 reacting the final solution including  68 Gallium isotope with a peptide dissolved in a buffer at a pH between 3.5 and 3.9 to obtain a radiolabelled-peptide; 
 cooling the radiolabelled-peptide to a temperature below 40° C.; and 
 purifying the radiolabelled-peptide on a C18 column. 
 
     
     
         12 . A cassette for purifying and concentrating  68 Gallium isotope from an outlet of a target containing a target solution including zinc, comprising:
 a first conduit having a first end connected to an inlet of a strong cationic exchanger and a second end connected to a dilution vial, wherein the first conduit includes a first 3-way valve;   a first bottle, a second bottle, and a third bottle containing chemical reagents and connected to the first 3-way valve;   an outlet of the strong cationic exchanger connected by a second conduit to an elution vial, wherein the second conduit includes a second 3-way valve connected to a first waste vial;   a third conduit connecting the elution vial to an inlet of a strong anionic exchanger, wherein the third conduit includes a third 3-way valve;   a fourth bottle and a fifth bottle containing chemical reagents and connected to the third 3-way valve;   an outlet of the strong anionic exchanger connected by a fourth conduit to a final solution vial, wherein the fourth conduit includes a fourth 3-way valve connected to a second waste vial;   a sixth bottle containing water and connected to the dilution vial by a fifth conduit; and   a sixth conduit connecting the dilution vial to the outlet of the target.   
     
     
         13 . The cassette of  claim 12 , wherein the elution vial is connected to a seventh bottle containing hydrochloric acid. 
     
     
         14 . The cassette of  claim 12 , wherein the first conduit further includes a fifth 3-way valve, the first and second bottles are connected to the first 3-way valve, and the third bottle is connected to the fifth 3-way valve. 
     
     
         15 . (canceled) 
     
     
         16 . The process according to  claim 1 , wherein the irradiated target solution is diluted at least  10  volume times with water. 
     
     
         17 . The process according to  claim 3 , wherein the strong anion exchanger is preconditioned with hydrochloric acid solution before feeding the complemented solution into the strong anion exchanger. 
     
     
         18 . A cassette for a device that synthesizes radiopharmaceuticals products from chemical reagents, comprising:
 a first conduit having a first end connected to an inlet of a strong cationic exchanger and a second end connected to a dilution vial, wherein the first conduit includes a first 3-way valve;   a first bottle, a second bottle, and a third bottle containing chemical reagents and connected to the first 3-way valve;   an outlet of the strong cationic exchanger connected by a second conduit to an elution vial, wherein the second conduit includes a second 3-way valve connected to a first waste vial;   a third conduit connecting the elution vial to an inlet of a strong anionic exchanger, wherein the third conduit includes a third 3-way valve;   a fourth bottle and a fifth bottle containing chemical reagents and connected to the third 3-way valve;   an outlet of the strong anionic exchanger connected by a fourth conduit to a final solution vial, wherein the fourth conduit includes a fourth 3-way valve connected to a second waste vial;   a sixth bottle containing water and connected to the dilution vial by a fifth conduit; and   a sixth conduit connecting the dilution vial to an outlet of a target containing a target solution including zinc.   
     
     
         19 . The cassette of  claim 18 , wherein the elution vial is connected to a seventh bottle containing hydrochloric acid. 
     
     
         20 . The cassette of  claim 18  wherein:
 the first conduit further includes a fifth 3-way valve; 
 the first and second bottles are connected to the first 3-way valve; and 
 the third bottle is connected to the fifth 3-way valve.