The present disclosure encompasses heterodimeric compositions for delivering radiolabeled and other ligands to a cell or tissue, and particularly to compositions and methods of use thereof for targeting and imaging cells and tissues expressing both an integrin and gastrin-releasing peptide receptor, in particular prostate cancer cells. The disclosure, therefore, firstly encompasses compositions that can comprise a heterodimeric probe comprising a first peptide domain comprising a moiety capable of selectively binding to an integrin; a second peptide domain comprising a moiety capable of selectively binding to a gastrin-releasing peptide receptor; a linker connecting the first peptide domain and the second peptide domain; and a prosthetic group. The first peptide domain comprises at least one tripeptide comprising the amino acid sequence of arginine-glycine-aspartate, and the second domain can be the peptide bombesin(7-14). The prosthetic group can be the fluoride isotope
18
F so that the heterodimeric probe may be detected by positron emission tomography or by single photon emission computed tomography, or a metal radionuclide. The radionuclide may be attached to the probe via a chelating tether.
本公开涵盖了用于将放射性标记和其他
配体传递到细胞或组织的异源二聚体组合物,特别是用于定位和成像表达整合素和胃泌素释放肽受体的细胞和组织的组合物及其使用方法。因此,首先涵盖了可以包括异源二聚体探针的组合物,该异源二聚体探针包括第一肽结构域,其中包括能够选择性结合整合素的结构域;第二肽结构域,其中包括能够选择性结合胃泌素释放肽受体的结构域;连接第一肽结构域和第二肽结构域的连接物;以及一个假体基团。第一肽结构域包括至少一个三肽,其
氨基酸序列为精
氨酸-甘
氨酸-
天冬氨酸,第二结构域可以是肽骨胃素(7-14)。假体基团可以是
氟同位素18F,以便通过正电子发射断层扫描或单光子发射计算机断层扫描,或
金属放射性同位素来检测异源二聚体探针。放射性同位素可以通过螯合连接物连接到探针上。