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

Abstract

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 (18)F-labeled heterodimers showed significantly better microPET imaging quality than (18)F-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 (18)F-labeled heterodimer ((18)F-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.

• Authors: Yongjun Yan, Kai Chen, Min Yang, Xilin Sun, Shuanglong Liu, Xiaoyuan Chen
• Journal: Amino acids (Amino Acids) Vol. 41 Issue 2 Pg. 439-47 (Jul 2011) ISSN: 1438-2199 [Electronic] Austria
• PMID: 20936525 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Cross-Linking Reagents
• Fluorine Radioisotopes
• Integrin alphaVbeta3
• Peptides, Cyclic
• Radiopharmaceuticals
• Receptors, Bombesin
• beta-Alanine
• Bombesin

Topics

• Animals
• Binding, Competitive
• Bombesin (analogs & derivatives, chemical synthesis, pharmacokinetics, pharmacology)
• Cell Line, Tumor
• Cross-Linking Reagents (chemistry)
• Fluorine Radioisotopes (pharmacokinetics, pharmacology)
• Humans
• Integrin alphaVbeta3 (metabolism)
• Kidney (diagnostic imaging)
• Liver (diagnostic imaging)
• Male
• Mice
• Mice, Nude
• Muscle, Skeletal (diagnostic imaging)
• Neoplasm Transplantation
• Peptides, Cyclic (chemical synthesis, pharmacokinetics, pharmacology)
• Positron-Emission Tomography (methods)
• Prostatic Neoplasms (diagnostic imaging)
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics, pharmacology)
• Receptors, Bombesin (metabolism)
• beta-Alanine (analogs & derivatives, chemistry)