| 摘要 |
The present invention relates to probes for use in the detection, imaging, diagnosis, targeting, treatment, etc. of cancers expressing the gastrin releasing peptide receptor (GRPR). For example, such probes may be molecules conjugated to detectable labels which are preferably moieties suitable for detection by gamma imaging and SPECT or by positron emission tomography (PET) or magnetic resonance imaging (MRI) or fluorescence spectroscopy or optical imaging methods. |
| 主权项 |
1. A GRPR-antagonist of the general formula:
MC-S—Pwherein:
at least one (radio)metal (M) and a chelator (C) which stably binds M; alternatively MC may represent a Tyr- or a prosthetic group carrying a (radio)halogen; S is an optional spacer covalently linked between the N-terminal of P and C and may be selected to provide a means for (radio)halogenation; P is a GRP receptor peptide antagonist of the general formula:
Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-CO—Z Xaa1 is not present or is selected from the group consisting of amino acid residues Asn, Thr, Phe, 3-(2-thienyl)alanine (Thi), 4-chlorophenylalanine (Cpa), α-naphthylalanine (α-Nal), β-naphthylalanine (13-Nal), 1,2,3,4-tetrahydronorharman-3-carboxylic acid (Tpi), Tyr, 3-iodo-tyrosine (o-I-Tyr), Trp, pentafluorophenylalanine (5-F-Phe) (all as L- or D-isomers);
Xaa2 is Gln, Asn, HisXaa3 is Trp, 1,2,3,4-tetrahydronorharman-3-carboxylic acid (Tpi)Xaa4 is Ala, Ser, ValXaa5 is Val, Ser, ThrXaa6 is Gly, sarcosine (Sar), D-Ala, β-AlaXaa7 is His, (3-methyl)histidine (3-Me)His Z is selected from —NHOH, —NHNH2, —NH-alkyl, —N(alkyl)2, or —O-alkyl or wherein X is NH (amide) or O (ester) and R1 and R2 are the same or different and selected from a proton, a (substituted)alkyl, a (substituted) alkyl ether, an aryl, an aryl ether or an alkyl-, halogen, hydroxyl or hydroxyalkyl substituted aromatic group. |
