JP2018515543A - 放射性医薬品を調製する複数の合成プロセスを連続して行う方法、この方法を行うためのデバイスおよびカセット - Google Patents
放射性医薬品を調製する複数の合成プロセスを連続して行う方法、この方法を行うためのデバイスおよびカセット Download PDFInfo
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- 150000001450 anions Chemical class 0.000 claims description 27
- 239000003480 eluent Substances 0.000 claims description 22
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 16
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- 238000012546 transfer Methods 0.000 claims description 9
- 238000007865 diluting Methods 0.000 claims description 3
- 238000011065 in-situ storage Methods 0.000 claims description 3
- HIIJZYSUEJYLMX-UHFFFAOYSA-N 1-fluoro-3-(2-nitroimidazol-1-yl)propan-2-ol Chemical compound FCC(O)CN1C=CN=C1[N+]([O-])=O HIIJZYSUEJYLMX-UHFFFAOYSA-N 0.000 claims description 2
- AOYNUTHNTBLRMT-MXWOLSILSA-N 2-Deoxy-2(F-18)fluoro-2-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H]([18F])C=O AOYNUTHNTBLRMT-MXWOLSILSA-N 0.000 claims description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 2
- PAXWQORCRCBOCU-LURJTMIESA-N 6-fluoro-L-dopa Chemical compound OC(=O)[C@@H](N)CC1=CC(O)=C(O)C=C1F PAXWQORCRCBOCU-LURJTMIESA-N 0.000 claims 1
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
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- XLYOFNOQVPJJNP-NJFSPNSNSA-N ((18)O)water Chemical compound [18OH2] XLYOFNOQVPJJNP-NJFSPNSNSA-N 0.000 description 3
- 238000012864 cross contamination Methods 0.000 description 3
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- 238000006460 hydrolysis reaction Methods 0.000 description 3
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
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- QZZYPHBVOQMBAT-LRAGLOQXSA-N (2s)-2-amino-3-[4-(2-fluoranylethoxy)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OCC[18F])C=C1 QZZYPHBVOQMBAT-LRAGLOQXSA-N 0.000 description 2
- KDLLNMRYZGUVMA-ZYMZXAKXSA-N (8r,9s,13s,14s,16r,17r)-16-fluoranyl-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H]([18F])C4)O)[C@@H]4[C@@H]3CCC2=C1 KDLLNMRYZGUVMA-ZYMZXAKXSA-N 0.000 description 2
- HIIJZYSUEJYLMX-JZRMKITLSA-N 1-fluoranyl-3-(2-nitroimidazol-1-yl)propan-2-ol Chemical compound [18F]CC(O)CN1C=CN=C1[N+]([O-])=O HIIJZYSUEJYLMX-JZRMKITLSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-BJUDXGSMSA-N ac1l2y5h Chemical compound [18FH] KRHYYFGTRYWZRS-BJUDXGSMSA-N 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000001307 helium Substances 0.000 description 2
- 229910052734 helium Inorganic materials 0.000 description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
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- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
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- 239000002245 particle Substances 0.000 description 2
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- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 2
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- LSSQMISUDUUZCC-DWSYCVKZSA-N (2,5-dioxopyrrolidin-1-yl) 4-fluoranylbenzoate Chemical compound C1=CC([18F])=CC=C1C(=O)ON1C(=O)CCC1=O LSSQMISUDUUZCC-DWSYCVKZSA-N 0.000 description 1
- UXCAQJAQSWSNPQ-ZIVQXEJRSA-N 1-[(2r,4s,5r)-4-fluoranyl-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H]([18F])C1 UXCAQJAQSWSNPQ-ZIVQXEJRSA-N 0.000 description 1
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- PAXWQORCRCBOCU-RPDRGXCHSA-N 6-((18)F)fluoro-L-dopa Chemical compound OC(=O)[C@@H](N)CC1=CC(O)=C(O)C=C1[18F] PAXWQORCRCBOCU-RPDRGXCHSA-N 0.000 description 1
- 206010073306 Exposure to radiation Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical group [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- OIBDVHSTOUGZTJ-PEBLQZBPSA-N [(2r,3r,4s,5s,6s)-3,4,6-triacetyloxy-5-(trifluoromethylsulfonyloxy)oxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@@H](OS(=O)(=O)C(F)(F)F)[C@@H](OC(C)=O)[C@@H]1OC(C)=O OIBDVHSTOUGZTJ-PEBLQZBPSA-N 0.000 description 1
- CEGXZKXILQSJHO-PMMAARTGSA-N [18F]C(=O)C[C@@H](O)[C@@H](O)[C@H](O)CO Chemical compound [18F]C(=O)C[C@@H](O)[C@@H](O)[C@H](O)CO CEGXZKXILQSJHO-PMMAARTGSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
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- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
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- PBVFROWIWWGIFK-KWCOIAHCSA-N fluoromethylcholine (18F) Chemical compound [18F]C[N+](C)(C)CCO PBVFROWIWWGIFK-KWCOIAHCSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
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- 239000013067 intermediate product Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
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- 239000002184 metal Substances 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
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- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 1
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- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
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Abstract
Description
a)18Fを含んだ水を提供するステップと、
b)ステップa)において提供された水から18Fを陰イオン交換物質上にトラップするステップと、
c)トラップされた18Fを陰イオン交換物質から第1の放射性医薬品合成カセットの反応槽へ溶離するステップと、
d)第1の放射性医薬品合成カセットを用いて、溶離された18Fを取り込んだ放射性医薬品を調製するステップと
を備える第1の合成運転を実施するステップを備え、
ステップa)〜d)は、別の放射性医薬品合成カセットを用いた少なくとも1つのその後の運転において繰り返され、
本方法は、2つの連続した運転の間に前記陰イオン交換物質のリコンディショニング・ステップを備える。
18F−FDG ([18F]−フルオロ−2−ジオキシグルコース)、
FMISO (1−(2−ニトロ−イミダゾリル)−3−[18F]−フルオロ−2−プロパノール);1H−1−(3−[18F]−フルオロ−2−ヒドロキシプロピル)−2−ニトロイミダゾール)、
NaF (ナトリウム[18F]−フルオリド)、
18F−FLT (3’−ジオキシ−3’−[18F]フルオロチミジン):
18F−FET (O−(2−[18F]−フルオロエチル)−L−チロシン)
18F−FES (16α−[18F]フルオロ−17 β−エストラジオール)、
FCHOL ([18F]フルオロコリン)
FACETATE ([18F]フルオロアセタート)
FDGal ([18F]フルオロデオキシガラクトース)
F DOPA (L−6−[18F]フルオロ−3,4−ジヒドロキシフェニルアラニン)
18SFB (N−スクシンイミジル4−[18F]フルオロベンゾアート)。
フレームまたは筺体
18Fを含んだ水を導入するための入口、
前記入口へ接続された、陰イオン交換物質を備える陰イオン交換器、
前記陰イオン交換器へ接続された、溶離剤を備える溶離剤容器、
前記陰イオン交換器へ接続された、リコンディショニング剤を備えるリコンディション容器、
溶離された18Fを放射性医薬品合成カセットへ選択的に供給するための分配手段、
各カセットが前記分配手段へ接続された、少なくとも2つの放射性医薬品合成カセット
を備える。
本発明によるデバイスへ接続可能であり、かつそれによって操作可能な複数のバルブが設けられた少なくとも1つのマニホールド
陰イオン交換物質を備える陰イオン交換器、
溶離剤を備える溶離剤容器
リコンディショニング剤を備えるリコンディション容器
を備える。
Claims (10)
- 放射性医薬品を調製する複数の合成プロセスを連続して行う方法であって、前記方法は、
a)18Fを含んだ水を提供するステップと、
b)ステップa)において提供された前記水から前記18Fを陰イオン交換物質(18)上にトラップするステップと、
c)前記トラップされた18Fを前記陰イオン交換物質(18)から第1の放射性医薬品合成カセット(50’)の反応槽(58)へ溶離するステップと、
d)前記第1の放射性医薬品合成カセット(50’)を用いて、前記溶離された18Fを取り込んだ放射性医薬品を調製するステップと
を備える第1の合成運転を実施するステップを備え、
ステップa)〜d)は、別の放射性医薬品合成カセット(50”、50”’)を用いた少なくとも1つのその後の運転において繰り返され、
前記方法は、2つの連続した運転の間に前記陰イオン交換物質(18)のリコンディショニング・ステップを備える、
方法。 - 前記陰イオン交換物質(18)は、第四級アンモニウム陰イオン交換物質である、請求項1に記載の方法。
- 前記リコンディショニング・ステップは、炭酸塩溶液を用いて前記陰イオン交換物質を処理するステップを備える、請求項1または請求項2に記載の方法。
- 前記炭酸塩溶液は、濃縮された炭酸塩溶液を水で希釈することによってその場で調製される、請求項3に記載の方法。
- ステップc)において溶離剤が相間移動剤を含む、請求項1〜4のいずれか一項の記載の方法。
- 前記放射性医薬品は、FDG、FMISO、NaF、FLT、FET、FES、FCHOL、FACETATE、FDGal、FDOPA、SFBの群から選択される、請求項1〜5のいずれか一項の記載の方法。
- 前記複数の合成プロセスのうちの少なくとも1つのプロセスは、18FDGを調製するステップを備える、請求項1〜6のいずれか一項の記載の方法。
- 特に請求項1〜7のいずれか一項に記載の方法による、放射性医薬品を調製する複数の合成プロセスを連続して行うためのデバイス(48)であって、前記デバイスは、
フレーム(49)
18Fを含んだ水を導入するための入口(16j)、
前記入口(16j)へ接続された、陰イオン交換物質を備える陰イオン交換器(18)、
前記陰イオン交換器(18)へ接続された、溶離剤を備える溶離剤容器(26)、
前記陰イオン交換器(18)へ接続された、リコンディショニング剤を備えるリコンディション容器(32)、
溶離された18Fを放射性医薬品合成カセット(50)へ選択的に供給するための分配手段(16f、16g、16h)、
各カセット(50’、50”、50”’)が前記分配手段(16f、16g、16h)へ接続された少なくとも2つの放射性医薬品合成カセット(50’、50”、50”’)
を備える、デバイス(48)。 - 請求項8に記載のデバイスに用いるカセット(10)であって、前記カセットは、
請求項8に記載のデバイスに接続可能であり、かつそれによって操作可能な複数のバルブ(16)が設けられた少なくとも1つのマニホールド(12,14)、
陰イオン交換物質を備える陰イオン交換器(18)、
溶離剤を備える溶離剤容器(26)、
リコンディショニング剤を備えるリコンディション容器(32)
を備えるカセット(10)。 - 前記リコンディション容器(32)は、濃縮された炭酸塩溶液を含み、前記カセット(10)は、水を備える水容器(34)も設けられた、請求項9に記載のカセット。
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