JP2022515989A - ガリウム68を生成および/または精製するプロセスおよびシステム - Google Patents
ガリウム68を生成および/または精製するプロセスおよびシステム Download PDFInfo
- Publication number
- JP2022515989A JP2022515989A JP2021532410A JP2021532410A JP2022515989A JP 2022515989 A JP2022515989 A JP 2022515989A JP 2021532410 A JP2021532410 A JP 2021532410A JP 2021532410 A JP2021532410 A JP 2021532410A JP 2022515989 A JP2022515989 A JP 2022515989A
- Authority
- JP
- Japan
- Prior art keywords
- acid solution
- cation exchange
- solution
- exchange column
- resin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 99
- GYHNNYVSQQEPJS-YPZZEJLDSA-N Gallium-68 Chemical compound [68Ga] GYHNNYVSQQEPJS-YPZZEJLDSA-N 0.000 title abstract description 11
- 239000012535 impurity Substances 0.000 claims abstract description 23
- 229910052751 metal Inorganic materials 0.000 claims abstract description 18
- 239000002184 metal Substances 0.000 claims abstract description 18
- 239000002253 acid Substances 0.000 claims description 109
- 239000011347 resin Substances 0.000 claims description 45
- 229920005989 resin Polymers 0.000 claims description 45
- 239000013522 chelant Substances 0.000 claims description 38
- 229920001577 copolymer Polymers 0.000 claims description 38
- 238000005341 cation exchange Methods 0.000 claims description 35
- 239000007787 solid Substances 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 29
- 239000003480 eluent Substances 0.000 claims description 27
- 239000007788 liquid Substances 0.000 claims description 21
- 238000010828 elution Methods 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 16
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- 238000002600 positron emission tomography Methods 0.000 claims description 13
- 238000003384 imaging method Methods 0.000 claims description 11
- 229940010982 dotatate Drugs 0.000 claims description 10
- QVFLVLMYXXNJDT-CSBVGUNJSA-N (2s,3r)-2-[[(4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-7-[(1r)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-19-[[(2r)-3-phenyl-2-[[2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]pro Chemical compound C([C@H](C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC1=O)C(=O)N[C@@H]([C@H](O)C)C(O)=O)NC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1)C1=CC=CC=C1 QVFLVLMYXXNJDT-CSBVGUNJSA-N 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 9
- 238000011084 recovery Methods 0.000 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 239000003729 cation exchange resin Substances 0.000 claims description 6
- 239000012217 radiopharmaceutical Substances 0.000 claims description 6
- 229940121896 radiopharmaceutical Drugs 0.000 claims description 6
- 230000002799 radiopharmaceutical effect Effects 0.000 claims description 6
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 5
- 229960002700 octreotide Drugs 0.000 claims description 5
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 4
- 108010043958 Peptoids Proteins 0.000 claims description 4
- 229910001385 heavy metal Inorganic materials 0.000 claims description 4
- 238000000163 radioactive labelling Methods 0.000 claims description 4
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 3
- 238000004140 cleaning Methods 0.000 claims description 3
- 238000007865 diluting Methods 0.000 claims description 3
- 229920006026 co-polymeric resin Polymers 0.000 claims description 2
- 230000001678 irradiating effect Effects 0.000 claims description 2
- 230000002934 lysing effect Effects 0.000 claims description 2
- 239000012607 strong cation exchange resin Substances 0.000 claims description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims 1
- 238000005277 cation exchange chromatography Methods 0.000 abstract description 52
- HCHKCACWOHOZIP-AKLPVKDBSA-N zinc-68 Chemical compound [68Zn] HCHKCACWOHOZIP-AKLPVKDBSA-N 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 145
- 239000011701 zinc Substances 0.000 description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
- XOYLJNJLGBYDTH-UHFFFAOYSA-M chlorogallium Chemical compound [Ga]Cl XOYLJNJLGBYDTH-UHFFFAOYSA-M 0.000 description 23
- 238000000746 purification Methods 0.000 description 23
- 238000004090 dissolution Methods 0.000 description 20
- 229910021654 trace metal Inorganic materials 0.000 description 18
- 230000009089 cytolysis Effects 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000012498 ultrapure water Substances 0.000 description 11
- 238000005259 measurement Methods 0.000 description 7
- -1 polyacryllate Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 239000002585 base Substances 0.000 description 6
- 238000002372 labelling Methods 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- XBJPSVQFCQFGDC-WSCOIBMGSA-K 2-[4-[2-[[(2R)-1-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-4-[[(1S,2R)-1-carboxy-2-hydroxypropyl]carbamoyl]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxylatomethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate gallium-68(3+) Chemical compound [68Ga+3].C[C@@H](O)[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](Cc2ccccc2)NC(=O)CN2CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(O)=O XBJPSVQFCQFGDC-WSCOIBMGSA-K 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 239000000356 contaminant Substances 0.000 description 5
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 239000004793 Polystyrene Substances 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229920002223 polystyrene Polymers 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000012045 crude solution Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229910052750 molybdenum Inorganic materials 0.000 description 3
- 239000011733 molybdenum Substances 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000010979 pH adjustment Methods 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- 108700017638 DOTA-Tyr(3)- octreotide Proteins 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 101100208721 Mus musculus Usp5 gene Proteins 0.000 description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052787 antimony Inorganic materials 0.000 description 2
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052788 barium Inorganic materials 0.000 description 2
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 2
- 239000003637 basic solution Substances 0.000 description 2
- 229910052790 beryllium Inorganic materials 0.000 description 2
- ATBAMAFKBVZNFJ-UHFFFAOYSA-N beryllium atom Chemical compound [Be] ATBAMAFKBVZNFJ-UHFFFAOYSA-N 0.000 description 2
- 229910052797 bismuth Inorganic materials 0.000 description 2
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052793 cadmium Inorganic materials 0.000 description 2
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 2
- 229940023913 cation exchange resins Drugs 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 238000010668 complexation reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000008472 epithelial growth Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 229910052732 germanium Inorganic materials 0.000 description 2
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000011133 lead Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 201000011519 neuroendocrine tumor Diseases 0.000 description 2
- 238000009206 nuclear medicine Methods 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 229960003330 pentetic acid Drugs 0.000 description 2
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229910052711 selenium Inorganic materials 0.000 description 2
- 239000011669 selenium Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- ITWBWJFEJCHKSN-UHFFFAOYSA-N 1,4,7-triazonane Chemical compound C1CNCCNCCN1 ITWBWJFEJCHKSN-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- JHALWMSZGCVVEM-UHFFFAOYSA-N 2-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]acetic acid Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CC1 JHALWMSZGCVVEM-UHFFFAOYSA-N 0.000 description 1
- PZCJTYVWTGPGOH-OKVMNLLFSA-N 2-[4-[2-[[(2R)-1-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-4-[[(2R,3R)-1,3-dihydroxybutan-2-yl]carbamoyl]-7-[(1R)-1-hydroxyethyl]-13-(1H-indol-3-ylmethyl)-16-(naphthalen-1-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound C[C@@H](O)[C@@H](CO)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](Cc2ccccc2)NC(=O)CN2CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC2)C(=O)N[C@@H](Cc2cccc3ccccc23)C(=O)N[C@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 PZCJTYVWTGPGOH-OKVMNLLFSA-N 0.000 description 1
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 1
- 229910017855 NH 4 F Inorganic materials 0.000 description 1
- 206010052399 Neuroendocrine tumour Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- LBYWTNBGUBZKJM-UHFFFAOYSA-N OP(=C)=O Chemical compound OP(=C)=O LBYWTNBGUBZKJM-UHFFFAOYSA-N 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229960000958 deferoxamine Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- KPVWDKBJLIDKEP-UHFFFAOYSA-L dihydroxy(dioxo)chromium;sulfuric acid Chemical compound OS(O)(=O)=O.O[Cr](O)(=O)=O KPVWDKBJLIDKEP-UHFFFAOYSA-L 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 238000001730 gamma-ray spectroscopy Methods 0.000 description 1
- 238000000084 gamma-ray spectrum Methods 0.000 description 1
- 229960005219 gentisic acid Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- MEFBJEMVZONFCJ-UHFFFAOYSA-N molybdate Chemical compound [O-][Mo]([O-])(=O)=O MEFBJEMVZONFCJ-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 208000016065 neuroendocrine neoplasm Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 239000012487 rinsing solution Substances 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 238000004724 ultra fast liquid chromatography Methods 0.000 description 1
- 238000001195 ultra high performance liquid chromatography Methods 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/083—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins the peptide being octreotide or a somatostatin-receptor-binding peptide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J39/00—Cation exchange; Use of material as cation exchangers; Treatment of material for improving the cation exchange properties
- B01J39/04—Processes using organic exchangers
- B01J39/05—Processes using organic exchangers in the strongly acidic form
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J39/00—Cation exchange; Use of material as cation exchangers; Treatment of material for improving the cation exchange properties
- B01J39/26—Cation exchangers for chromatographic processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J45/00—Ion-exchange in which a complex or a chelate is formed; Use of material as complex or chelate forming ion-exchangers; Treatment of material for improving the complex or chelate forming ion-exchange properties
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J47/00—Ion-exchange processes in general; Apparatus therefor
- B01J47/02—Column or bed processes
- B01J47/026—Column or bed processes using columns or beds of different ion exchange materials in series
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J49/00—Regeneration or reactivation of ion-exchangers; Apparatus therefor
- B01J49/60—Cleaning or rinsing ion-exchange beds
-
- G—PHYSICS
- G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
- G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
- G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
- G21G1/001—Recovery of specific isotopes from irradiated targets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B6/00—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
- A61B6/02—Devices for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
- A61B6/03—Computerised tomographs
- A61B6/037—Emission tomography
-
- G—PHYSICS
- G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
- G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
- G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
- G21G1/04—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators
- G21G1/10—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators by bombardment with electrically charged particles
-
- G—PHYSICS
- G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
- G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
- G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
- G21G1/001—Recovery of specific isotopes from irradiated targets
- G21G2001/0021—Gallium
-
- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
- H05H6/00—Targets for producing nuclear reactions
Abstract
Description
非限定的な一実施形態による68Gaの生成および/または精製に使用することができるプロセス100のフローチャートを図1に示す。最初に、68Znを含むターゲットに加速陽子ビームを照射する。ターゲットは、液体形態でも固体形態でもよい。固体形態の場合、68Znを含む固体ターゲットを適切な支持体に圧縮し、次いで、当業者に既知の方法に従って、ステップ102で陽子ビームを照射してよい(固体の照射済みターゲットが形成される)。照射することができる68Znの量(質量)は、50mg~2500mgの間、好ましくは100mg~250mgの間であり得る。液体形態の場合、68Znを含む液体ターゲット(すなわち、溶液)に、当業者に既知の方法に従って、ステップ103で粒子ビームを直接照射してよい(照射済み液体ターゲットが形成される)。液体ターゲットは、特に、68Zn塩を含み得る。適切なZn塩はZn(NO3)2であるが、他の実施形態では他の適切な塩を使用してもよい。任意の適切な体積の液体ターゲットに照射してもよい。一実施形態では、照射される液体ターゲットの体積は、1mL~7mLの間、好ましくは1.5mL~2mLの間を含み得る。照射の結果、さらに後述するように、68Gaならびに他の放射性核種(例えば、66Ga、67Ga、67Zn、および66Zn)が生成される。
さらに図1に関して、pH調整ステップ105または106の後に、68Znの照射生成物の溶液を用意する。溶液は、特に、68Znおよび68Ga(ならびに任意選択で他の放射性核種および金属不純物)を含む。次いで、68Znの照射生成物の溶液を、ステップ108で第1のキレート陽イオン交換クロマトグラフィカラムに添加する。具体的には、68Znの照射生成物の溶液を、ポリマー(通常、樹脂の形態)と接触させる。任意の理論に拘泥するものではないが、68Gaならびに68Znはポリマーに吸着されるが、それぞれの吸着の度合い(すなわち、68Ga、68Znとカラムとの間のイオン相互作用の強さ)は異なる。さらに後述するように、洗浄液および溶離液を慎重に選択することによって、68Gaを実質的に溶離させることなく、68Znを最初にクロマトグラフィから溶離させることができる。したがって、これにより、68Gaを68Znと分離し、最終的には回収することができる。別の言い方をすれば、ステップ108は、68Znとは対照的に、68Gaがポリマーと会合するのに有利な条件下で行われる。
Alves, F., Alves, V.H., Neves, A.C.B., Do Carmo, S.J.C., Nactergal, B., Hellas, V., Kral, E., Goncalves-Gameiro, C., Abrunhosa, A.J., 2017. Cyclotron production of Ga-68 for human use from liquid targets: From theory to practice. AIP Conf. Proc. 1845. https://doi.org/10.1063/1.4983532
Blaser, J.P., Boehm, F., Marmier, P., Peaslee, D.C., 1950. Fonctions d’excitation de la reaction (p,n). (I). Helv. Phys. Acta 24, 3-38.
Hermanne, A., 1997. Evaluated cross section and thick target yield data of Zn+P processes for practical applications Private communication. Exfor: D4093 49
Howe, H.A., 1958. (p,n) Cross Sections of Copper and Zinc. Phys. Rev. 109, 6-8
Lin, M., Waligorski, G.J., Lepera, C.G., 2018. Production of curie quantities of 68Ga with a medical cyclotron via the 68Zn(p,n)68Ga reaction. Appl. Radiat. Isot. 133, 1-3. https://doi.org/10.1016/j.apradiso.2017.12.010
Mueller, D., Klette, I., Baum, R.P., Gottschaldt, M., Schultz, M.K., Breeman, W.A.P., 2012. Simplified NaCl based68Ga concentration and labeling procedure for rapid synthesis of68Ga radiopharmaceuticals in high radiochemical purity. Bioconjug. Chem. 23, 1712-1717. https://doi.org/10.1021/bc300103t
Nortier, F.M., Stevenson, N.R., Gelbart, W.Z., 1995. Investigation of the thermal performance of solid targets for radioisotope production. Nucl. Instruments Methods Phys. Res. Sect. A Accel. Spectrometers, Detect. Assoc. Equip. 355, 236-241. https://doi.org/10.1016/0168-9002(94)01110-9
Pandey, M.K., Byrne, J.F., Jiang, H., Packard, A.B., Degrado, T.R., 2014. Cyclotron production of 68Ga via the 68Zn(p,n)68Ga reaction in aqueous solution. Am. J. Nucl. Med. Mol. Imaging 4, 303-310.
Szelecsenyi, F., Boothe, T. e., Takacs, S., Tarkanyi, F., Tavano, E., 1998. Evaluated Cross Section and Thick Target Yield Data Bases of Zn + p Processes for Practical Applications. Appl. Radiat. Isot. 49, 1005-1032.
Velikyan, I., 2015. 68Ga-based radiopharmaceuticals: Production and application relationship, Molecules. https://doi.org/10.3390/molecules200712913
Verel, I., Visser, G.W.M., Boellaard, R., Marijke, ;, Walsum, S.-V., Snow, G.B., Van Dongen, G.A.M.S., 2003. 89 Zr Immuno-PET: Comprehensive Procedures for the Production of 89 Zr-Labeled Monoclonal Antibodies. J Nucl Med 44, 1271-1281.
202 シリンジ
204 溶解バイアル
206 シリンジ
2071 第1のバルブ
2072 第2のバルブ
208 第1のキレート陽イオン交換クロマトグラフィカラム
209 バイアル
210 バイアル
211 バイアル
212 バイアル
213 バイアル
214 第2のコポリマー陽イオン交換クロマトグラフィカラム
216 バイアル
218 生成物バイアル
Claims (51)
- サイクロトロンで生成した68Gaを精製するプロセスであって、
(a)68Znと68Gaとの混合物を含む溶液を用意するステップと、
(b)溶液を、ヒドロキサマート樹脂を含む第1のキレート陽イオン交換カラムと接触させるステップと、
(c)ステップ(b)の後に得られた第1のキレート陽イオン交換カラムを洗浄して、洗浄済みの第1のキレート陽イオン交換カラムを得るステップと、
(d)洗浄済みの第1のキレート陽イオン交換カラムから68Gaを溶離させて、第1の溶離液を得るステップと、
(e)第1の溶離液を、樹脂を含む第2のコポリマー陽イオン交換カラムと接触させるステップと、
(f)ステップ(e)の後に第2のコポリマー陽イオン交換カラムを洗浄して、洗浄済みの第2のコポリマー陽イオン交換カラムを得るステップと、
(g)洗浄済みの第2のコポリマー陽イオン交換カラムから68Gaを溶離させて、精製済み68Gaを含む第2の溶離液を得るステップとを含む、プロセス。 - 第1のキレート陽イオン交換カラムを洗浄するステップが、第1の酸溶液を第1のキレート陽イオン交換カラムと接触させることを含む、請求項1に記載のプロセス。
- 第1の酸溶液が、0.01NのHCl溶液である、請求項2に記載のプロセス。
- 洗浄済みの第1のキレート陽イオン交換カラムから68Gaを溶離させるステップが、第2の酸溶液を洗浄済みの第1のキレート陽イオン交換カラムと接触させることを含む、請求項1から3のいずれか一項に記載のプロセス。
- 第2の酸溶液が、第1の酸溶液を超える規定度を有する、請求項4に記載のプロセス。
- 第2の酸溶液が、0.75NのHCl溶液である、請求項5に記載のプロセス。
- 第1の溶離液を第2のコポリマー陽イオン交換カラムと接触させる前に、第1の溶離液を第3の酸溶液で希釈するステップをさらに含む、請求項1から6のいずれか一項に記載のプロセス。
- 第3の酸溶液が、第1の溶液と実質的に同様の規定度を有する、請求項7に記載のプロセス。
- 第3の酸溶液が、0.01NのHCl溶液である、請求項8に記載のプロセス。
- 第2のコポリマー陽イオン交換カラムを洗浄するステップが、第4の酸溶液を第2のコポリマー陽イオン交換カラムと接触させることを含む、請求項1から9のいずれか一項に記載のプロセス。
- 第4の酸溶液が、第1の酸溶液または第3の酸溶液と実質的に同様の規定度を有する、請求項10に記載のプロセス。
- 第4の酸溶液が、0.01NのHCl溶液である、請求項11に記載のプロセス。
- 洗浄済みの第2のコポリマー陽イオン交換カラムから68Gaを溶離させるステップが、塩を含む第5の酸溶液を第2のコポリマー陽イオン交換カラムと接触させることを含む、請求項1から12のいずれか一項に記載のプロセス。
- 塩を含む第5の酸溶液が、第1の酸溶液を超える規定度を有する、請求項13に記載のプロセス。
- 第5の酸溶液が、5.5NのHClである、請求項14に記載のプロセス。
- 第5の酸溶液が、5MのNaCl溶液である、請求項14または15に記載のプロセス。
- コポリマー樹脂が、2種の官能基に結合されたシリカ骨格を含む、請求項1から16のいずれか一項に記載のプロセス。
- 官能基が、C8基およびベンゼンスルホン酸である、請求項17に記載のプロセス。
- 樹脂が、CUBCX123樹脂である、請求項18に記載のプロセス。
- ステップ(a)の前に、Znを含むターゲットに加速粒子ビームを照射するステップをさらに含む、請求項1から20のいずれか一項に記載のプロセス。
- 加速粒子ビームが、サイクロトロンで生成される、請求項20に記載のプロセス。
- Znを含むターゲットが、液体ターゲットであり、照射済み液体ターゲットが、68Znと68Gaとの混合物を含む溶液である、請求項20または21に記載のプロセス。
- Znを含むターゲットが、固体ターゲットである、請求項20または21に記載のプロセス。
- 照射済み固体ターゲットを溶解酸に溶解して、68Znと68Gaとの混合物を含む溶液を形成するステップをさらに含む、請求項23に記載のプロセス。
- 照射済み固体ターゲットを溶解するステップが、照射済み固体ターゲットを第6の酸溶液と接触させることを含む、請求項24に記載のプロセス。
- 第6の酸溶液が、第1の酸溶液または第3の酸溶液を超える規定度を有する、請求項25に記載のプロセス。
- 第6の酸溶液が、7NのHNO3溶液である、請求項26に記載のプロセス。
- 第6の酸溶液が、少なくとも1.5のpHを有する、請求項27に記載のプロセス。
- ステップ(b)の前に、68Znと68Gaとの混合物を含む溶液のpHを調整するステップをさらに含む、請求項25から28のいずれか一項に記載のプロセス。
- pHを1~3の間に調整する、請求項29に記載のプロセス。
- pHを約2に調整する、請求項30に記載のプロセス。
- pHを第7の酸溶液で調整する、請求項29から31のいずれか一項に記載のプロセス。
- 第6の酸溶液が、2.5MのNH4HCO2溶液である、請求項32に記載のプロセス。
- 第2の溶離液中の68Gaの全体の回収収率が、少なくとも80%である、請求項1から33のいずれか一項に記載のプロセス。
- 第2の溶離液は、68Gaの有効モル放射能が少なくとも20GBq/μmolである、請求項1から33のいずれか一項に記載のプロセス。
- 68Gaを精製するシステムであって、
・ヒドロキサマート樹脂を含む第1のカラムと、
・コポリマー強陽イオン交換樹脂を含む第2のカラムと、
・請求項1から35のいずれか一項に記載のプロセスに従って68Gaを精製するための制御器とを含む、システム。 - 陽イオン交換樹脂が、2種の官能基に結合されたシリカ骨格を含む、請求項36に記載のシステム。
- 官能基が、C8基およびベンゼンスルホン酸である、請求項37に記載のシステム。
- 陽イオン交換樹脂が、CUBCX123樹脂である、請求項38に記載のシステム。
- 2%未満の67Gaおよび66Gaを有する、68Gaを含む組成物。
- 請求項1から35のいずれか一項に記載のプロセスによって、または請求項36から39のいずれか一項に記載のシステムを使用することによって得られる、請求項40に記載の組成物。
- 10ppm未満の金属不純物および20ppm未満の重金属を有する、請求項41または42に記載の組成物。
- 担体分子をさらに含み、担体分子が68Gaで放射性標識されている、請求項40から43のいずれか一項に記載の組成物。
- 担体分子が、ペプチド、ペプトイド、またはペプチド模倣薬である、請求項43に記載の組成物。
- ペプチド、ペプトイド、またはペプチド模倣薬が、ポジトロン放射断層撮影法(PET)イメージングのための放射性医薬である、請求項44に記載の組成物。
- ペプチドが、1,4,7,10-テトラアザシクロドデカン-1,4,7,10-四酢酸-Tyr(3)-Tyr(8)-オクトレオチド(DOTA-TATE)である、請求項45に記載の組成物。
- 68GaによるDOTA-TATEの放射性標識効率が、少なくとも92%である、請求項46に記載の組成物。
- 担体分子が、ヒト組織を標的とする、請求項43から47のいずれか一項に記載の組成物。
- ヒト組織が、甲状腺、脳、胃腸、膵臓、脾臓、腎臓、神経内分泌腫瘍、腎細胞癌、小細胞肺がん、乳がん、前立腺がん、および悪性リンパ腫からなる群から選択される、請求項48に記載の組成物。
- ポジトロン放射断層撮影法(PET)イメージングのための、請求項40から49のいずれか一項に記載の組成物の使用。
- ポジトロン放射断層撮影法(PET)イメージングをそれを必要とする対象に行う方法であって、対象にPETを施す前に、イメージング量の請求項40から49のいずれか一項に記載の組成物を対象に投与するステップを含む、方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862777994P | 2018-12-11 | 2018-12-11 | |
US62/777,994 | 2018-12-11 | ||
PCT/CA2019/051777 WO2020118426A1 (en) | 2018-12-11 | 2019-12-10 | Processes and systems for producing and/or purifying gallium-68 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022515989A true JP2022515989A (ja) | 2022-02-24 |
JP7402233B2 JP7402233B2 (ja) | 2023-12-20 |
Family
ID=71075908
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021532410A Active JP7402233B2 (ja) | 2018-12-11 | 2019-12-10 | ガリウム68を生成および/または精製するプロセスおよびシステム |
Country Status (6)
Country | Link |
---|---|
US (1) | US20220044835A1 (ja) |
EP (1) | EP3893944A4 (ja) |
JP (1) | JP7402233B2 (ja) |
AU (1) | AU2019399674A1 (ja) |
CA (1) | CA3122862A1 (ja) |
WO (1) | WO2020118426A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20220093127A (ko) * | 2019-10-12 | 2022-07-05 | 에이알티엠에스 프로덕츠, 인크. | 갈륨-68의 분리 시스템 및 방법 |
CN113019279A (zh) * | 2021-03-11 | 2021-06-25 | 山西医科大学第一医院 | 一种放射性药物制备的自动合成装置及其使用方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1210099C (zh) | 2003-04-22 | 2005-07-13 | 万荣联丰特种树脂材料有限公司 | 一种吸附镓专用螯合树脂及制备方法 |
DE102010037964B3 (de) | 2010-10-05 | 2012-03-22 | ITM Isotopen Technologien München AG | 68Ga-Generator |
WO2015175972A2 (en) | 2014-05-15 | 2015-11-19 | Mayo Foundation For Medical Education And Research | Solution target for cyclotron production of radiometals |
EP3101660B1 (en) | 2015-06-05 | 2017-08-09 | Universidade de Coimbra | Process for producing gallium-68 through the irradiation of a solution target |
JP6770837B2 (ja) | 2016-06-28 | 2020-10-21 | 日本メジフィジックス株式会社 | 放射性フッ素標識有機化合物を製造する方法 |
EP3503929B1 (en) * | 2016-08-26 | 2022-02-23 | Mayo Foundation for Medical Education and Research | Rapid isolation of cyclotron-produced gallium-68 |
US11197938B1 (en) * | 2016-10-19 | 2021-12-14 | Battelle Memorial Institute | System and process for production of isotopes and isotope compositions |
US20180322972A1 (en) | 2017-05-04 | 2018-11-08 | General Electric Company | System and method for making a solid target within a production chamber of a target assembly |
-
2019
- 2019-12-10 AU AU2019399674A patent/AU2019399674A1/en active Pending
- 2019-12-10 EP EP19895524.7A patent/EP3893944A4/en active Pending
- 2019-12-10 CA CA3122862A patent/CA3122862A1/en active Pending
- 2019-12-10 WO PCT/CA2019/051777 patent/WO2020118426A1/en unknown
- 2019-12-10 JP JP2021532410A patent/JP7402233B2/ja active Active
- 2019-12-10 US US17/413,146 patent/US20220044835A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
JP7402233B2 (ja) | 2023-12-20 |
WO2020118426A1 (en) | 2020-06-18 |
AU2019399674A1 (en) | 2021-06-24 |
EP3893944A1 (en) | 2021-10-20 |
US20220044835A1 (en) | 2022-02-10 |
CA3122862A1 (en) | 2020-06-18 |
EP3893944A4 (en) | 2022-10-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11266975B2 (en) | Solution target for cyclotron production of radiometals | |
US20160358683A1 (en) | Process for producing gallium-68 through the irradiation of a solution target | |
US11417439B2 (en) | Rapid isolation of cyclotron-produced gallium-68 | |
WO2019183724A1 (en) | Systems, apparatus and methods for separating actinium, radium, and thorium | |
US20180158559A1 (en) | Method and system for producing gallium-68 radioisotope by solid targeting in a cyclotron | |
JP7402233B2 (ja) | ガリウム68を生成および/または精製するプロセスおよびシステム | |
Randhawa et al. | Meitner-auger electron emitters for targeted radionuclide therapy: mercury-197m/g and antimony-119 | |
JP2011505376A (ja) | 68Ga系放射性医薬品の比放射能を向上させるための68Ge/68Gaジェネレータ溶出液のFe(III)からの精製 | |
JP2009229201A (ja) | Gaのイオンを単離する方法とそのための装置 | |
US20220351873A1 (en) | Systems and methods of isolation of gallium-68 | |
US8932876B2 (en) | Method and system for purifying charged radioisotopes | |
Fonseca et al. | GMP-Automated Purification of Copper-61 Produced in Cyclotron Liquid Targets: Methodological Aspects | |
RU2522892C1 (ru) | Способ получения активной фармацевтической субстанции для синтеза препаратов галлия-68 | |
Chuvilin et al. | Synthesis and investigation of a preparation based on 212Pb-labeled DOTATATE synthetic peptide for therapy of neuroendocrine tumors | |
EP4276855A1 (en) | Production method for ac-225 solution and production method for medicine using ac-225 solution | |
Bubenshchikov et al. | The impact of zirconium‐89 solution formulation on the efficiency of [89Zr] Zr‐deferoxamine synthesis | |
Ruiz Quiros | A Chromatographic Method to Separate Sc (III) from Zn (II) Ions: A Step in the Purification of Sc-44 (an isotope of medical interest) | |
Charles | Production of High Specific Activity Rhenium-186 for Radiotherapeutic Applications and Reformulation of a Novel Liquid Brachytherapy Agent | |
JP2023540498A (ja) | 非担体添加銅-64の調製のための精製プロセス | |
Ulin et al. | Method for obtaining 68Ga | |
Lesik et al. | Comparison of Different Methods for the Analysis of Octreotide Derivatives Labeled with Gallium-68 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210611 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220127 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220201 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220916 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230828 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230905 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231027 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20231114 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20231208 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7402233 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |