Title:
ペプチダーゼ結合部分と結合しペプチダーゼ発現組織及び器官をイメージングする放射性イメージング部分
Document Type and Number:
Japanese Patent JP2010502646
Kind Code:
A
Abstract:
Conjugates, methods and kits are described for imaging tissues and organs that express one or more peptidases. In a preferred embodiment of the invention, a series of di-(2-pyridylmethyl)amine (D) ligands, which can bind M(CO)3+ [M=Tc or Re], were coupled to lisinopril (L). Aliphatic tethers with varying number of methylene groups (3, 4, 5, and 7; D(C4)L, D(C5)L, D(C6)L, and D(C8)L, respectively) were utilized, with in vitro inhibitory activity increasing with increasing number of methylene groups. The D(C8)L conjugate was observed to be significantly more potent than D(C4)L. In vivo specificity for ACE was studied in both tissue distribution and gamma imaging studies, demonstrating localization in tissues with high ACE content. Localization was blocked by pretreatment with lisinopril.
Inventors:
Babich, Jay., W.
Eckerman, W.
Femia, F., Jay.
Zimmerman, Craig
Eckerman, W.
Femia, F., Jay.
Zimmerman, Craig
Application Number:
JP2009526898A
Publication Date:
January 28, 2010
Filing Date:
August 29, 2007
Export Citation:
Assignee:
Biostream Therapeutics Incorporated
International Classes:
A61K31/555; A61K31/444; A61K51/00; A61P9/04; A61P9/10; A61P9/12; A61P11/00; A61P13/12; A61P29/00; A61P35/00; A61P43/00; C07D401/14
Domestic Patent References:
| JP2005521736A | 2005-07-21 | |||
| JP2005538751A | 2005-12-22 | |||
| JP2005521736A | 2005-07-21 | |||
| JP2005538751A | 2005-12-22 | |||
| JP2005519957A | 2005-07-07 |
Foreign References:
| WO2004091669A1 | 2004-10-28 | |||
| US5601801A | 1997-02-11 | |||
| WO2004091669A1 | 2004-10-28 |
Other References:
JPN6012051916; Ｓｔｅｐｈｅｎｓｏｎ ＫＡ ｅｔ ａｌ．: 'Ａ ｃｏｎｖｅｎｉｅｎｔ ｓｏｌｉｄ-ｐｈａｓｅ ｓｙｎｔｈｅｓｉｓ ｍｅｔｈｏｄｏｌｏｇｙ ｆｏｒ ｐｒｅｐａｒｉｎｇ ｐｅｐｔｉｄｅ-ｄｅｒｉｖｅｄ ｍｏｌｅｃｕｌａｒ ｉｍａｇｉｎｇ ａｇｅｎｔ' Ｃａｎ． Ｊ． Ｃｈｅｍ． Ｖｏｌ．８３, 2005, ｐｐ．２０６０-２０６６
JPN6012051910; Ｆｅｍｉａ ＦＪ ｅｔ ａｌ．: 'Ｎｏｖｅｌ Ｍ（ＣＯ）３＋ ［Ｍ＝Ｔｃ，Ｒｅ］ ｃｏｎｔａｉｎｉｎｇ ｄｅｒｉｖａｔｉｖｅｓ ｏｆ ｌｉｓｉｎｏｐｒｉｌ ｆｏｒ ｉｍａｇｉｎｇ ａｎｇｉｏｔｅｎｓｉｎ ｃｏｎｖｅｒｔｉｎｇ ｅｎｚｙ' Ｔｅｃｈｎｅｔｉｕｍ， Ｒｈｅｎｉｕｍ ａｎｄ Ｏｔｈｅｒ Ｍｅｔａｌｓ ｉｎ Ｃｈｅｍｉｓｔｒｙ ａｎｄ Ｎｕｃｌｅａｒ Ｍｅｄｉｃｉｎｅ Ｖｏｌ．７, 20060101, ｐｐ．６２７-６３０
JPN6012051910; Ｆｅｍｉａ ＦＪ ｅｔ ａｌ．: 'Ｎｏｖｅｌ Ｍ（ＣＯ）３＋ ［Ｍ＝Ｔｃ，Ｒｅ］ ｃｏｎｔａｉｎｉｎｇ ｄｅｒｉｖａｔｉｖｅｓ ｏｆ ｌｉｓｉｎｏｐｒｉｌ ｆｏｒ ｉｍａｇｉｎｇ ａｎｇｉｏｔｅｎｓｉｎ ｃｏｎｖｅｒｔｉｎｇ ｅｎｚｙ' Ｔｅｃｈｎｅｔｉｕｍ， Ｒｈｅｎｉｕｍ ａｎｄ Ｏｔｈｅｒ Ｍｅｔａｌｓ ｉｎ Ｃｈｅｍｉｓｔｒｙ ａｎｄ Ｎｕｃｌｅａｒ Ｍｅｄｉｃｉｎｅ Ｖｏｌ．７, 20060101, ｐｐ．６２７-６３０
JPN6012051913; Ｓｈｉｒａｎｉ Ｊ ｅｔ ａｌ．: 'Ｉｍａｇｉｎｇ ｔｈｅ ｒｅｎｉｎ-ａｎｇｉｏｔｅｎｓｉｎ- ａｌｄｏｓｔｅｒｏｎｅ ｓｙｓｔｅｍ ｉｎ ｔｈｅ ｈｅａｒｔ．' Ｃｕｒｒ Ｈｅａｒｔ Ｆａｉｌ Ｒｅｐ． Ｖｏｌ．２ Ｎｏ．２, 200508, ｐｐ．７８-８６
JPN6012051916; Ｓｔｅｐｈｅｎｓｏｎ ＫＡ ｅｔ ａｌ．: 'Ａ ｃｏｎｖｅｎｉｅｎｔ ｓｏｌｉｄ-ｐｈａｓｅ ｓｙｎｔｈｅｓｉｓ ｍｅｔｈｏｄｏｌｏｇｙ ｆｏｒ ｐｒｅｐａｒｉｎｇ ｐｅｐｔｉｄｅ-ｄｅｒｉｖｅｄ ｍｏｌｅｃｕｌａｒ ｉｍａｇｉｎｇ ａｇｅｎｔ' Ｃａｎ． Ｊ． Ｃｈｅｍ． Ｖｏｌ．８３, 2005, ｐｐ．２０６０-２０６６
JPN6012051910; Ｆｅｍｉａ ＦＪ ｅｔ ａｌ．: 'Ｎｏｖｅｌ Ｍ（ＣＯ）３＋ ［Ｍ＝Ｔｃ，Ｒｅ］ ｃｏｎｔａｉｎｉｎｇ ｄｅｒｉｖａｔｉｖｅｓ ｏｆ ｌｉｓｉｎｏｐｒｉｌ ｆｏｒ ｉｍａｇｉｎｇ ａｎｇｉｏｔｅｎｓｉｎ ｃｏｎｖｅｒｔｉｎｇ ｅｎｚｙ' Ｔｅｃｈｎｅｔｉｕｍ， Ｒｈｅｎｉｕｍ ａｎｄ Ｏｔｈｅｒ Ｍｅｔａｌｓ ｉｎ Ｃｈｅｍｉｓｔｒｙ ａｎｄ Ｎｕｃｌｅａｒ Ｍｅｄｉｃｉｎｅ Ｖｏｌ．７, 20060101, ｐｐ．６２７-６３０
JPN6012051910; Ｆｅｍｉａ ＦＪ ｅｔ ａｌ．: 'Ｎｏｖｅｌ Ｍ（ＣＯ）３＋ ［Ｍ＝Ｔｃ，Ｒｅ］ ｃｏｎｔａｉｎｉｎｇ ｄｅｒｉｖａｔｉｖｅｓ ｏｆ ｌｉｓｉｎｏｐｒｉｌ ｆｏｒ ｉｍａｇｉｎｇ ａｎｇｉｏｔｅｎｓｉｎ ｃｏｎｖｅｒｔｉｎｇ ｅｎｚｙ' Ｔｅｃｈｎｅｔｉｕｍ， Ｒｈｅｎｉｕｍ ａｎｄ Ｏｔｈｅｒ Ｍｅｔａｌｓ ｉｎ Ｃｈｅｍｉｓｔｒｙ ａｎｄ Ｎｕｃｌｅａｒ Ｍｅｄｉｃｉｎｅ Ｖｏｌ．７, 20060101, ｐｐ．６２７-６３０
JPN6012051913; Ｓｈｉｒａｎｉ Ｊ ｅｔ ａｌ．: 'Ｉｍａｇｉｎｇ ｔｈｅ ｒｅｎｉｎ-ａｎｇｉｏｔｅｎｓｉｎ- ａｌｄｏｓｔｅｒｏｎｅ ｓｙｓｔｅｍ ｉｎ ｔｈｅ ｈｅａｒｔ．' Ｃｕｒｒ Ｈｅａｒｔ Ｆａｉｌ Ｒｅｐ． Ｖｏｌ．２ Ｎｏ．２, 200508, ｐｐ．７８-８６
JPN6012051916; Ｓｔｅｐｈｅｎｓｏｎ ＫＡ ｅｔ ａｌ．: 'Ａ ｃｏｎｖｅｎｉｅｎｔ ｓｏｌｉｄ-ｐｈａｓｅ ｓｙｎｔｈｅｓｉｓ ｍｅｔｈｏｄｏｌｏｇｙ ｆｏｒ ｐｒｅｐａｒｉｎｇ ｐｅｐｔｉｄｅ-ｄｅｒｉｖｅｄ ｍｏｌｅｃｕｌａｒ ｉｍａｇｉｎｇ ａｇｅｎｔ' Ｃａｎ． Ｊ． Ｃｈｅｍ． Ｖｏｌ．８３, 2005, ｐｐ．２０６０-２０６６
Attorney, Agent or Firm:
Tomijio Sasashima
Moriaki Ogawa
Kunio Araki
Moriaki Ogawa
Kunio Araki