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Relevant academic research and scientific papers

A new 18F-labeled BBN-RGD peptide heterodimer with a symmetric linker for prostate cancer imaging

A peptide heterodimer comprises two different receptor-targeting peptide ligands. Molecular imaging probes based on dual-receptor targeting peptide heterodimers exhibit improved tumor targeting efficacy for multi-receptor expressing tumors compared with their parent single-receptor targeting peptide monomers. Previously we have developed bombesin (BBN)-RGD (Arg-Gly-Asp) peptide heterodimers, in which BBN and RGD are covalently connected with an asymmetric glutamate linker (J Med Chem 52:425-432, 2009). Although 18F-labeled heterodimers showed significantly better microPET imaging quality than 18F-labeled RGD and BBN monomers in a PC-3 xenograft model which co-expresses gastrin-releasing peptide receptor (GRPR) and integrin αvβ3, tedious heterodimer synthesis due to the asymmetric nature of glutamate linker restricts their clinical applications. In this study, we report the use of a symmetric linker AEADP [AEADP = 3,3′-(2-aminoethylazanediyl) dipropanoic acid] for the synthesis of BBN-RGD peptide heterodimer. The 18F-labeled heterodimer (18F-FB-AEADP-BBN-RGD) showed comparable microPET imaging results with glutamate linked BBN-RGD heterodimers, indicating that the replacement of glutamate linker with AEADP linker did not affect the biological activities of BBN-RGD heterodimer. The heterodimer synthesis is rather easy and straightforward. Because tumors often co-express multiple receptors, the use of a symmetric linker provides a general method of fast assembly of various peptide heterodimers for imaging multi-receptor expressing tumors.

RADIOLABELED BBN-RGD HETERODIMERS FOR CANCER TARGETING

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 18F 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.