Claims for Patent: 9,375,498

Summary for Patent: 9,375,498

Title:	Process for the preparation of complexes of .sup.68Ga
Abstract:	A process for the preparation of complexes containing .sup.68Ga wherein a buffer formic acid/formate in the presence of compounds capable to sequester metal cations is used in the complexion reaction.
Inventor(s):	Fugazza; Lorenza (San Fiorano, IT), Filannino; Maria Azzurra (Bertinoro, IT), Mariani; Maurizio Franco (Ivrea, IT)
Assignee:	Advanced Accelerator Applications S.A. (Saint Genis Pouilly, FR)
Application Number:	14/237,728
Patent Claims:	1. Process for the preparation of complexes of .sup.68Ga wherein the complexing reaction between a chelator-functionalized molecule and .sup.68Ga is carried out in a buffer formic acid/formate aqueous solution optionally in the presence of a compound capable of sequestering metal cations, wherein said compound able to sequester metal cations, if used, is added at the beginning of the complexing reaction. 2. A process according to claim 1 wherein the complexing reaction between a chelator-functionalized molecule and .sup.68Ga is carried out in a buffered aqueous solution in the presence of a compound capable of sequestering metal cations. 3. A process according to claim 1 wherein said chelator-functionalized molecule is selected from the group consisting of: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tretraacetic acid ("DOTA"), 1,4,7-triazacyclononane-1,4,7-triyltriacetic acid ("NOTA") and, 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacet- ic acid ("PCTA") while said formate is sodium formate. 4. A process according to claim 1 wherein the ratio formic acid/formate in the buffer is between 1 and 3.5. 5. A process according to claim 1 wherein said compound capable of sequestering metal cations is selected from the group consisting of: glycine and other chelating aminoacids, crown ethers and nitrogen crown ethers, eterocyclic organic compound, calixarenes, polydentate chelator, natural chelating agents, catechins, tannin, porphyrinin, and linear or macrocyclic chelating agents. 6. A process according to claim 1 wherein the complexing reaction is carried out in a pH range between 3 and 4.5. 7. A process according to claim 6 wherein the reaction pH is between 3.2 and 4.2. 8. A process according to claim 6 wherein the reaction pH is between 3.4 and 4.0. 9. Process according to claim 1 wherein: a commercial generator of .sup.68Ga is eluted with an eluate containing an acid directly into a vial containing buffer formate and a base; a chelator-functionalized molecule is added into the vial and the reaction vial is heated for a short time; the product is collected. 10. Process according to claim 1 wherein: a commercial generator of .sup.68Ga is eluted with an eluate containing an acid directly into a vial containing a chelator-functionalized molecule; buffer formate and a base are added into the vial and the reaction vial is heated for a short time; the product is collected. 11. Process according to claim 7 wherein the acid eluate is an aqueous solution of HCl, while the base is an aqueous solution of NaOH. 12. A reaction kit comprising: a vial containing the chelator-functionalized molecule and a compound capable of sequestering metal cations; a vial or a syringe containing a suitable ultra-pure formic acid/sodium formate mixture. 13. A vial containing a chelator-functionalized molecule, a selected compound capable of sequestering metal cations and a suitable ultra-pure formic acid/sodium formate mixture. 14. A reaction kit according to claim 12 wherein said vials are siliconized vials. 15. Complexes of .sup.68Ga, obtained by the process according to claim 1, characterized in that they contain less than 10 mg/ml formate/formic acid and, if used, less than 100 nmols of the compound capable of sequestering metal cations. 16. A process according to claim 1 wherein said chelator-functionalized molecule is chosen from the group consisting of: DOTA, NOTA, and PCTA while said formate is sodium formate. 17. A process according to claim 1 wherein the ratio of formic acid/formate in the buffer is between 1 and 3.5.