Gastrin releasing peptide compounds 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2009143101 A2 2009-11-26 [WO2009143101]WO2009143101 A3 2010-01-14 [WO2009143101] / 2009-11-262010-01-14
申请号/申请日
2009WO-US44447 / 2009-05-19
发明人
LATTUADA LUCIANO;CAPPELLETTI ENRICO;LINDER KAREN E;NUNN ADRIAN D;LANTRY LAURA;
申请人
BRACCO IMAGING;
主分类号
IPC分类号
A01N-037/18A61K-038/00
摘要
(WO2009143101) Methods and compositions for diagnosing, staging disease, monitoring therapeutic effect of drugs and imaging a patient are provided, including radiopharmaceutical formulations.  Compositions comprising Ga-AMBA complexed with a radioactive isotope are provided; as are methods of imaging Gastrin Releasing Peptide receptor (GRP-R) bearing tissue and methods of diagnosing or staging disease in patients suspected of having disease associated with aberrant GRP-R function.  Further, methods of monitoring therapeutic effect of a drug targeted to a receptor that crosstalks with GRP-R are provided; as are methods of pre-dosing/co-dosing non-target tissues containing GRP-R.  Particularly, methods of monitoring activity of receptors and receptor pathways in vivo/in vitro by using a ligand that binds to the GRP-R are provided; as are methods of measuring the activity of a receptor or group of receptors and their associated pathways that exhibit crosstalk with the GRP-R by using such a ligand which is also detectable by external means.
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
地址
代理人
代理机构
;
优先权号
2008US-61054335 2008-05-19
主权利要求
(WO2009143101) We claim: 1. A composition comprising L70 of formula: complexed with a radioactive isotope of Ga. 2. The composition of claim 2, wherein the radioactive isotope is (68)Ga. 3. A radiopharmaceutical formulation comprising the composition of claim 1, a buffer and selenomethionine. 4. The radiopharmaceutical composition of claim 3, wherein the buffer comprises sodium acetate. 5. The radiopharmaceutical formulation of any one of claims 3 or 4, further comprising ascorbic acid, EDTA and saline. 6. A method of imaging GRP-R bearing tissue in a patient comprising the steps of : a) administering a composition of any one of claims 1, 2 or 3 to a patient; and b) imaging the patient. 7. The method of imaging of claim 6, wherein the patient is imaged using PET. 8. A method of diagnosing or staging the disease of a patient suspected of having a disease associated with aberrant GRP-R function comprising the steps of:a) administering a composition of any one of claims 1, 2 or 3 to a patient; and b) imaging the patient. 9. The method of diagnosing or staging a disease of claim 8, wherein the patient is imaged using PET. 10. The method of any one of claims 6 or 8, further comprising administering a second GRP receptor targeting peptide, optionally conjugated to a linker and/or a chelator, to occupy GRP receptor binding sites in non-target tissue prior to administering the radiolabled composition in step a). 11. The method of any one of claim 6 or 8, further comprising administering in step a) a combination of: a) a first GRP receptor targeting peptide optionally conjugated to a linker and/or a chelator, to occupy GRP receptor binding sites in non-target tissue; and b) the radiolabeled compostion. 12. A method of monitoring the therapeutic effect of a drug targeted to a receptor that crosstalks with GRP-R comprising: a) administering to the patient a composition comprising a compound of general formula: M-N-O-P-G wherein M is an a metal chelator complexed with a metal radionuclide, or a moiety that contains a radiolabeled halogen such as F-, I-, I- or I-; N is absent, an alpha amino acid, a non-alpha amino acid with a cyclic group or other linking group; O is an alpha amino acid or a non-alpha amino acid with a cyclic group; P is absent, an alpha amino acid, a non-alpha amino acid with a cyclic group, or other linking group; and G is a GRP receptor targeting peptide, wherein at least one of N, O or P is a non-alpha amino acid with a cyclic group; b) imaging the patient; c) assessing the activity of the GRP-R based on the image; d) administering to the patient a drug which targets a receptor which crosstalks with GRP-R; e) administering to the patient a composition comprising a compound of general formula: M-N-O-P-G wherein M is an a metal chelator complexed with a metal radionuclide, or a moiety that contains a radiolabeled halogen such as F-, I-, I- or I-; N is 0, an alpha amino acid, a non-alpha amino acid with a cyclic group or other linking group; O is an alpha amino acid or a non-alpha amino acid with a cyclic group; P is 0, an alpha amino acid, a non-alpha amino acid with a cyclic group, or other linking group; and G is a GRP receptor targeting peptide, wherein at least one of N, O or P is a non-alpha amino acid with a cyclic group; f) imaging the patient; g) assessing the activity of the GRP-R based on the image; h) assessing the change in GRP-R activity after administration of the drug; and i) assessing the therapeutic effect of the drug based on the change in GRP-R activity. 13. The method of claim 12, further comprising altering the treatment regimen based on the assessed therapeutic effect of the drug. 14. The method of claim 12, wherein steps a)- c) occur up to about 30 days before step d). 15. The method of claim 14, wherein steps a)- c) occur about 15 days before step d). 16. The method of claim 15, wherein steps a)- c) occur about 7 days before step d). 17. The method of claim 12, wherein steps e) - i) occur within about 15 days of step d). 18. The method of claim 17, wherein steps e) - i) occur within about 7 days of step d). 19. The method of claim 12, wherein the method is repeated several times during the treatment process. 20. The method of claim 12, wherein the receptor that crosstalks with GRP-R is selected from the group consisting of the estrogen receptor and receptor tyrosine kinases (RTKs). 21. The method of claim 20, wherein the RTK is selected from the group consisting of EGFR, the Src family, HER2/ErbB3, Bcr-Abl, SCF, KIT, PDGF, VEGF-Rl, 2,3, FLT3, Ras, Raf, CSF-IR, and RET. 22. The method of claim 12, wherein the drug is selected from the group consisting of Exemestane, Lapatinib, Dasatinib, Gefitinib, Imatinib, Erlotinib, Sorafenib, Sunitinib, Anastrozole, Bortezomib, Tamoxifen, and .beta.2-estradiol. 23. The method of claim 12, wherein the compound of formula M-N-O-P-G is L70 of formula: complexed with a diagnostic radionuclide. 24. The method of claim 23 wherein L70 is complexed with a radionuclide detectable by PET. 25. The method of claim 23, wherein L70 is complexed with a radionuclide detectable by SPECT. 26. The method of claim 24, wherein L70 is complexed with (68)Ga. 27. The method of any one of claims 23 or 26, wherein the composition further comprises a buffer and selenomethionine. 28. The method of claim 27, wherein the buffer comprises sodium acetate. 29. The method of claim 27, wherein the composition further comprises ascorbic acid, EDTA and saline. 30. The method of claim 12, wherein the patient is imaged using PET. 31. The method of claim 12, wherein the patient is imaged using SPECT. 32. The method of claim 12, further comprising administering a second GRP receptor targeting peptide, optionally conjugated to a linker and/or a chelator, to occupy GRP receptor binding sites in non-target tissue prior to administering the composition in steps a) or e), or in steps a) and e),. 33. The method of claim 12, further comprising, in steps a) or e), or in steps a) and e), administering a combination of: a) a first GRP receptor targeting peptide optionally conjugated to a linker and/or a chelator, to occupy GRP receptor binding sites in non-target tissue; and b) the radiolabeled compostion.
法律状态
(WO2009143101) LEGAL DETAILS FOR WO2009143101  Actual or expected expiration date=2011-11-19    Legal state=DEAD    Status=LAPSED     Event publication date=2009-05-19  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2009044447  Application date=2009-05-19  Standardized application number=2009WO-US44447     Event publication date=2009-11-26  Event code=WO/A2  Event type=Examination events  International application published with declaration under Article 17 (2) (a)  Publication country=WO  Publication number=WO2009143101  Publication stage Code=A2  Publication date=2009-11-26  Standardized publication number=WO2009143101     Event publication date=2010-01-14  Event code=WO/A3  Event indicator=Pos  Event type=Examination events  Later publication of ISR with revised front page  Publication country=WO  Publication number=WO2009143101  Publication stage Code=A3  Publication date=2010-01-14  Standardized publication number=WO2009143101     Event publication date=2010-04-15  Event code=WO/DPE1  Event type=Examination events  Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)    Event publication date=2011-11-19  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE CN102076214  Actual or expected expiration date=2017-07-06    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=CN Corresponding appl: CN200980124446  Application date in the designated or member state=2009-05-19   Application number in the designated or member state=2009CN-80124446 Corresponding cc:  Designated or member state=CN Corresponding pat: CN102076214  Publication stage code in the designated or member state=A  Publication date in the designated or member state=2011-05-25   Publication number in the designated or member state=CN102076214    Event publication date=2011-07-06  Event code=CN/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=CN  LEGAL DETAILS FOR DESIGNATED STATE DE  Actual or expected expiration date=2010-11-20    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DE     Event publication date=2010-11-20  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=DE  LEGAL DETAILS FOR DESIGNATED STATE EP2291075  Actual or expected expiration date=2013-12-03    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=EP Corresponding appl: EP09751329  Application date in the designated or member state=2009-05-19   Application number in the designated or member state=2009EP-0751329 Corresponding cc:  Designated or member state=EP Corresponding pat: EP2291075  Publication stage code in the designated or member state=A2  Publication date in the designated or member state=2011-03-09   Publication number in the designated or member state=EP2291075    Event publication date=2010-01-20  Event code=WO/121  Event type=Designated states  EP: The EPO has been informed by wipo that ep was designated in this application Corresponding cc:  Designated or member state=EP     Event publication date=2014-06-04  Event code=EP/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=EP  LEGAL DETAILS FOR DESIGNATED STATE JP  Actual or expected expiration date=2029-05-19    Legal state=ALIVE    Status=PENDING   Corresponding cc:  Designated or member state=JP Corresponding appl: JP2011510636    Event publication date=2010-11-19  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=JP     Event publication date=2013-05-03  Event code=JP/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=JP  LEGAL DETAILS FOR DESIGNATED STATE US2013136691  Actual or expected expiration date=2029-05-19    Legal state=ALIVE    Status=PENDING   Corresponding cc:  Designated or member state=US Corresponding appl: US12993620  Application date in the designated or member state=2009-05-19   Application number in the designated or member state=2009US-12993620 Corresponding cc:  Designated or member state=US Corresponding pat: US2013136691  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2013-05-30   Publication number in the designated or member state=US20130136691    Event publication date=2011-06-07  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=US
专利类型码
A2A3
国别省市代码
若您需要申请原文,请登录。

最新评论

暂无评论。

登录后可以发表评论

意见反馈
返回顶部