JP2017501116A - 特にcck2受容体陽性腫瘍の診断および/または治療に使用するためのミニガストリン類似体 - Google Patents
特にcck2受容体陽性腫瘍の診断および/または治療に使用するためのミニガストリン類似体 Download PDFInfo
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- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
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Abstract
Description
PP−F10:DOTA−DGln−DGln−DGln−DGln−DGln−DGln−Ala−Tyr−Gly−Trp−Met−Asp−Phe−NH2
PP−F10N:DOTA−DGln−DGln−DGln−DGln−DGln−DGln−Ala−Tyr−Gly−Trp−Nle−Asp−Phe−NH2;
PP−F10 ox:DOTA−DGln−DGln−DGln−DGln−DGln−DGln−Ala−Tyr−Gly−Trp−Met(ox)−Asp−Phe−NH2。
HPLC分析のためのシステム:
システム:ポンプVarian Prostar 2030.01、ダイオードアレイ330.71、オートサンプラー410、 Packard Radiomatic Flow−One\
カラム:Stability 120 BS−C23 3μm 150×4.6mm、Dr.Maisch
グラジエント:
ポンプ1:Waters 515、ポンプ2:Hitachi L−7000、KnauerUV検出器K2510、放射線モニターEberline、インターフェースSS420X、EZstart
Rheodyneマニュアルインジェクター
カラム1:Stability 120 BS−C23 3μm 10×4.6mm、Dr.Maisch
カラム2:Stability 120 BS−C23 3μm 150×4.6mm、Dr.Maisch
Lu−177:ロット Lu−12−052−01/121042、活性 2GBq/200μl 0.04M HCL、itg(ITM AG)
PP−F11N:0.25mM H2O溶液
アンモニウム溶液:Sigma−Aldrich、金属不含
アスコルビン酸Na:Sigma−Aldrich
HCl 30%:Sigma−Aldrich、金属不含
H2O:Milipore system Biotelより
PPF−11Nを用いたLu−177の標識を、同位体:ペプチド比1:47で行った。
− 20μl Lu−177(190MBq)
− 5μl アスコルビン酸アンモニウム0.7M
− 50μl PPF−11N 0.25mM
− 5μl HC1 0.04M
この混合物を、95℃で20分間加熱した。
2つの標識反応を、2D HPLCに注入した。
第1のステップ:生成物をレオダインマニュアルインジェクターを用いてループに注入し、この生成物を第1のポンプを用いてカラム1を通じて押す。この生成物をループからカラム1へと移し、H2O+0.1TFAで洗浄する。
放射性標識化合物12MBqを、新鮮なヒト血漿2mL中でインキュベートした。試料40μLを、0、1、2、18、24、48および72時間後に採取し、かつMini−UniPrep Filter中に200μL(50%メタノールおよび50%アセトニトリル)を添加した。この溶液を、ボルテックス後に濾過する。濾過した溶液40μLをHPLCにより分析する。
CD1 nu/nuマウスに、5×106のA431細胞を注射した。CCK−2受容体陽性A431細胞1を一方の側腹部に注射し、かつ他方に非特異的対照としてmock細胞を注射した。腫瘍は、約10日後には約80〜120mgの重量に達する。放射性標識ペプチド150〜200kBq(5ピコモル)を、尾静脈に注射した。注射後所定の時点の後に、マウスをCO2窒息により殺した。器官を解剖し、秤量し、かつ放射能を測定した。1g当たりの%注入放射能(%i.A./g)を算出した。この動物実験は、現地の動物愛護委員会によって承認され、かつ国の規則に従って行ったものである。
Claims (9)
- CCK−2受容体関連疾患における診断的介入および/または治療的介入のためのミニガストリン類似体PP−F11であって、式:PP−F11−X−DGln−DGln−DGln−DGln−DGln−DGln−Ala−Tyr−Gly−Trp−Y−Asp−Phe−NH2[式中、Yは、メチオニンと置換されるアミノ酸を表し、かつXは、該ペプチドに結合した化学基を表す]を有する前記ミニガストリン類似体PP−F11。
- メチオニンがノルロイシンにより置換されている、請求項1に記載のミニガストリン類似体PP−F11。
- Xが、放射性核種、例えば177Luまたは90Yまたは111Inを表す、請求項1または2に記載のミニガストリン類似体PP−F11。
- Xが、光学活性な化学化合物を表す、請求項1から3までのいずれか1項に記載のミニガストリン類似体PP−F11。
- Xが、化学療法的活性化合物を表す、請求項1から4までのいずれか1項に記載のミニガストリン類似体PP−F11。
- Xがナノ粒子またはリポソームを表し、ここで、該ナノ粒子またはリポソームは、診断的機能を有する(例えば、光学活性剤またはMRI造影剤)か、またはそれ自体が治療的機能を有するか、または活性化合物が負荷されている、請求項1から5までのいずれか1項に記載のミニガストリン類似体PP−F11。
- CCK−2受容体関連疾患における診断的介入における、請求項1から6までのいずれか1項に記載のミニガストリンの使用。
- CCK−2受容体関連疾患における治療的介入における、請求項1から7までのいずれか1項に記載のミニガストリンの使用。
- メチオニンが、酸化電位を有しておらずかつ高い腫瘍親和性を示すメチオニン等配電子アミノ酸により置換されている、請求項8に記載のガストリン類似体の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP20130191807 EP2870972A1 (en) | 2013-11-06 | 2013-11-06 | Mini-gastrin analogue, in particular for use in CCK2 receptor positive tumour diagnosis and/or treatment |
EP13191807.0 | 2013-11-06 | ||
PCT/EP2014/072697 WO2015067473A1 (en) | 2013-11-06 | 2014-10-23 | Mini-gastrin analogue, in particular for use in cck2 receptor positive tumour diagnosis and/or treatment |
Related Child Applications (1)
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JP2018071479A Division JP6568618B2 (ja) | 2013-11-06 | 2018-04-03 | 特にcck2受容体陽性腫瘍の診断および/または治療に使用するためのミニガストリン類似体 |
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JP2017501116A true JP2017501116A (ja) | 2017-01-12 |
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JP2016528150A Ceased JP2017501116A (ja) | 2013-11-06 | 2014-10-23 | 特にcck2受容体陽性腫瘍の診断および/または治療に使用するためのミニガストリン類似体 |
JP2018071479A Active JP6568618B2 (ja) | 2013-11-06 | 2018-04-03 | 特にcck2受容体陽性腫瘍の診断および/または治療に使用するためのミニガストリン類似体 |
JP2019142770A Active JP6763069B2 (ja) | 2013-11-06 | 2019-08-02 | 特にcck2受容体陽性腫瘍の診断および/または治療に使用するためのミニガストリン類似体 |
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JP2018071479A Active JP6568618B2 (ja) | 2013-11-06 | 2018-04-03 | 特にcck2受容体陽性腫瘍の診断および/または治療に使用するためのミニガストリン類似体 |
JP2019142770A Active JP6763069B2 (ja) | 2013-11-06 | 2019-08-02 | 特にcck2受容体陽性腫瘍の診断および/または治療に使用するためのミニガストリン類似体 |
Country Status (18)
Country | Link |
---|---|
US (3) | US10130724B2 (ja) |
EP (2) | EP2870972A1 (ja) |
JP (3) | JP2017501116A (ja) |
KR (2) | KR20160070160A (ja) |
CN (1) | CN105705159B (ja) |
CY (1) | CY1120117T1 (ja) |
DK (1) | DK3065764T6 (ja) |
ES (1) | ES2670582T7 (ja) |
HR (1) | HRP20180631T1 (ja) |
HU (1) | HUE036943T2 (ja) |
LT (1) | LT3065764T (ja) |
NO (1) | NO3065764T3 (ja) |
PL (1) | PL3065764T6 (ja) |
PT (1) | PT3065764T (ja) |
RS (1) | RS57137B1 (ja) |
SI (1) | SI3065764T1 (ja) |
TR (1) | TR201802723T4 (ja) |
WO (1) | WO2015067473A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020522557A (ja) * | 2017-06-08 | 2020-07-30 | メディツィーニシェ・ウニヴェルジテート・インスブルックMedizinische Universitaet Innsbruck | 診断及び治療のための、改善された薬物動態及びコレシストキニン−2受容体(cck2r)への標的化 |
JP2020534327A (ja) * | 2017-09-21 | 2020-11-26 | パウル・シェラー・インスティトゥート | ミニガストリン誘導体、特にcck2受容体陽性腫瘍の診断及び/又は治療において使用するためのミニガストリン誘導体 |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2870972A1 (en) * | 2013-11-06 | 2015-05-13 | Paul Scherrer Institut | Mini-gastrin analogue, in particular for use in CCK2 receptor positive tumour diagnosis and/or treatment |
WO2018049129A1 (en) * | 2016-09-09 | 2018-03-15 | On Target Laboratories, LLC | Cholecystokinin 2 receptor targeted nir imaging and use thereof |
JPWO2019245038A1 (ja) | 2018-06-22 | 2021-07-08 | 株式会社Junten Bio | 複合状態を有する細胞混合物を用いた、免疫寛容を誘導する抗体、及び誘導されたリンパ球、また誘導されたリンパ球を用いる細胞治療剤及び治療法 |
TW202016312A (zh) | 2018-06-22 | 2020-05-01 | 日商順天生化股份有限公司 | 誘導免疫耐受之抗體、被誘導之淋巴球、及使用被誘導之淋巴球之細胞治療劑治療方法 |
CN112584843A (zh) | 2018-06-22 | 2021-03-30 | 顺天生化股份有限公司 | 用于诱发感染性免疫耐受的组合物 |
EP3868394A1 (en) * | 2020-02-20 | 2021-08-25 | Paul Scherrer Institut | Mono- and multi-triazolominigastrins for targeting of cck2r-positive neoplasms |
WO2021186060A1 (en) | 2020-03-20 | 2021-09-23 | Debiopharm International S.A. | Radiolabeled gastrin analogue for use in a method of treating and/or imaging cckb receptor positive diseases, in particular pulmonary and extrapulmonary small-cell carcinoma |
KR20230044463A (ko) | 2020-07-31 | 2023-04-04 | 폴 슈레 앙스띠뛰 | 갈륨-표지된 가스트린 유사체 및 cckb 수용체 양성 종양 또는 암의 영상화 방법에서의 용도 |
WO2022023541A1 (en) | 2020-07-31 | 2022-02-03 | Paul Scherrer Institut | Composition comprising a rapalog and a radiolabelled gastrin analogue, in particular for use in the treatment and/or diagnosis of cckb receptor positive cancer or tumors |
JP2023536267A (ja) | 2020-07-31 | 2023-08-24 | パウル・シェラー・インスティトゥート | アルファ放射標識ガストリンアナログおよびcckb受容体陽性疾患の処置方法におけるその使用 |
AU2021426543A1 (en) | 2021-02-02 | 2023-09-21 | Medizinische Universität Innsbruck | Improved cholecystokinin-2 receptor (cck2r) targeting for diagnosis and therapy |
WO2023051897A1 (en) | 2021-09-28 | 2023-04-06 | Debiopharm International S.A. | Method for predicting the response of a patient diagnosed with cancer to treatment and/or imaging with a compound targeting cck2-r, and compound for use in methods of selectively treating and/or imaging cancer |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4650787A (en) | 1985-04-25 | 1987-03-17 | Schally Andrew Victor | Biologically active octapeptides |
EP2870972A1 (en) * | 2013-11-06 | 2015-05-13 | Paul Scherrer Institut | Mini-gastrin analogue, in particular for use in CCK2 receptor positive tumour diagnosis and/or treatment |
-
2013
- 2013-11-06 EP EP20130191807 patent/EP2870972A1/en not_active Withdrawn
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2014
- 2014-10-23 WO PCT/EP2014/072697 patent/WO2015067473A1/en active Application Filing
- 2014-10-23 EP EP14795569.4A patent/EP3065764B3/en active Active
- 2014-10-23 CN CN201480061076.3A patent/CN105705159B/zh active Active
- 2014-10-23 HU HUE14795569A patent/HUE036943T2/hu unknown
- 2014-10-23 ES ES14795569T patent/ES2670582T7/es active Active
- 2014-10-23 NO NO14795569A patent/NO3065764T3/no unknown
- 2014-10-23 SI SI201430693T patent/SI3065764T1/en unknown
- 2014-10-23 LT LTEP14795569.4T patent/LT3065764T/lt unknown
- 2014-10-23 PT PT147955694T patent/PT3065764T/pt unknown
- 2014-10-23 US US15/034,943 patent/US10130724B2/en active Active
- 2014-10-23 PL PL14795569.4T patent/PL3065764T6/pl unknown
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- 2014-10-23 DK DK14795569.4T patent/DK3065764T6/da active
- 2014-10-23 RS RS20180451A patent/RS57137B1/sr unknown
- 2014-10-23 JP JP2016528150A patent/JP2017501116A/ja not_active Ceased
- 2014-10-23 KR KR1020167014687A patent/KR20160070160A/ko active IP Right Grant
- 2014-10-23 KR KR1020187022942A patent/KR102039930B1/ko active IP Right Grant
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- 2018-04-03 JP JP2018071479A patent/JP6568618B2/ja active Active
- 2018-04-19 HR HRP20180631TT patent/HRP20180631T1/hr unknown
- 2018-10-11 US US16/157,961 patent/US10953114B2/en active Active
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- 2019-08-02 JP JP2019142770A patent/JP6763069B2/ja active Active
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2020
- 2020-12-18 US US17/127,265 patent/US11623014B2/en active Active
Non-Patent Citations (4)
Title |
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AMINO ACIDS, vol. Vol.41, JPN6017023988, 2011, pages 1049 - 1058 * |
BIOPOLYMERS(PEPTIDE SCIENCE), vol. Vol.66, JPN6017023993, 2002, pages 399 - 418 * |
EUR J NUCL MED MOL IMAGING, vol. Vol.38, JPN6017023985, 2011, pages 1410 - 1416 * |
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Cited By (6)
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