公开(公告)号：US06872536B1

公开(公告)日：2005-03-29

申请号：US09437701

申请日：1999-11-10

申请人： David Roe ,  Christine Maria Ribic ,  Betty Chee-Ion Lawrence ,  Catherine Michelle Pollock ,  Alfred Pollack

发明人： David Roe ,  Christine Maria Ribic ,  Betty Chee-Ion Lawrence ,  Catherine Michelle Pollock ,  Alfred Pollack

IPC分类号： A61K51/08 ,  C07K7/02 ,  C07K7/06 ,  A61K38/04 ,  G01N33/53

CPC分类号： C07K7/06 ,  A61K51/08 ,  A61K51/088 ,  C07K7/02

摘要： Radiopharmaceuticals comprising molecules that target to N-formyl-methionyl-leucy-phenylalanine (fMLF) receptor on leukocytes in order to target sites of inflammation for diagnostic imaging are described. The targeting molecules are attached to capping groups that make the entire molecule either antagonists or weak agonists of fMLF receptor and therefore do not elicit a chemotactic response resulting in neutropenia. The preferred targeting molecule is ReO-Gly-lys(Dimethylgly-t-Butylgly-cys-gly)glu-trp-phe-leu-nle-NHCOcyclopropyl (wherein the peptide sequence NLeu-Leu-Phe-Trp-Glu-Lys-Gly is SEQ. ID No. 1.) The invention also relates to the use of combinatorial chemistry to obtain preferred molecules that target sites of inflammation for diagnostic imaging.

摘要翻译： 描述了包含靶向白细胞上的N-甲酰基 - 甲硫氨酰 - 亮氨酸 - 苯丙氨酸（fMLF）受体的分子，以靶向用于诊断成像的炎症部位的放射性药物。 靶向分子连接到使整个分子成为fMLF受体的拮抗剂或弱激动剂的封端基团，因此不引起导致中性粒细胞减少的趋化性反应。 优选的靶向分子是ReO-Gly-lys（Dimethylgly-t-Butylgly-cys-gly）glu-trp-phe-leu-nle-NHCO环丙基（其中肽序列NLeu-Leu-Phe-Trp-Glu-Lys-Gly 是SEQ ID NO No.1）。本发明还涉及组合化学的用途来获得靶向诊断成像炎症部位的优选分子。