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

Amino Acids. 2011 Jul;41(2):439-47. doi: 10.1007/s00726-010-0762-5. Epub 2010 Oct 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Binding, Competitive
  • Bombesin / analogs & derivatives*
  • Bombesin / chemical synthesis
  • Bombesin / pharmacokinetics
  • Bombesin / pharmacology
  • Cell Line, Tumor
  • Cross-Linking Reagents / chemistry
  • Fluorine Radioisotopes / pharmacokinetics
  • Fluorine Radioisotopes / 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
  • Peptides, Cyclic / pharmacokinetics
  • Peptides, Cyclic / pharmacology*
  • Positron-Emission Tomography / methods
  • Prostatic Neoplasms / diagnostic imaging*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / pharmacology*
  • Receptors, Bombesin / metabolism
  • beta-Alanine / analogs & derivatives
  • beta-Alanine / chemistry

Substances

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