18F-labeled BBN-RGD heterodimer for prostate cancer imaging.

Abstract

UNLABELLED:

Both bombesin (BBN) analogs and cyclic RGD peptides have been suitably radiolabeled for prostate cancer imaging. However, the limited expression of gastrin-releasing peptide receptor (GRPR) and integrin alpha(v)beta(3) as well as unfavorable in vivo kinetics limited further applications of these imaging agents. We hypothesize that a peptide ligand recognizing both GRPR and integrin will be advantageous because of its dual-receptor-targeting ability.

METHODS:

A BBN-RGD heterodimer was synthesized from bombesin(7-14) and c(RGDyK) through a glutamate linker and then labeled with (18)F via the N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB) prosthetic group. The receptor-binding characteristics and tumor-targeting efficacy of (18)F-FB-BBN-RGD were tested in vitro and in vivo.

RESULTS:

FB-BBN-RGD had comparable integrin alpha(v)beta(3)-binding affinity with c(RGDyK) and comparable GRPR-binding affinity with BBN(7-14). (18)F-FB-BBN-RGD had significantly higher tumor uptake compared with monomeric RGD and monomeric BBN peptide tracer analogs at all time points examined. The PC-3 tumor uptake of (18)F-FB-BBN-RGD was inhibited only partially in the presence of an excess amount of unlabeled BBN(7-14) or c(RGDyK) but was blocked completely in the presence of both BBN(7-14) and c(RGDyK). Compared with (18)F-FB-BBN and (18)F-FB-RGD, (18)F-FB-BBN-RGD also had improved pharmacokinetics, resulting in a significantly higher imaging quality.

CONCLUSION:

Dual integrin alpha(v)beta(3) and GRPR recognition showed significantly improved tumor-targeting efficacy and pharmacokinetics compared with (18)F-labeled RGD and BBN analogs. The same heterodimeric ligand design may also be applicable to other receptor system combinations and other imaging modalities.

• Authors: Zi-Bo Li, Zhanhong Wu, Kai Chen, Eun Kyoung Ryu, Xiaoyuan Chen
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 49 Issue 3 Pg. 453-61 (Mar 2008) ISSN: 0161-5505 [Print] United States
• PMID: 18287274 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• (18)F-FB-BBN-RGD
• Oligopeptides
• Radiopharmaceuticals
• Bombesin

Topics

• Animals
• Bombesin (analogs & derivatives, chemistry, pharmacokinetics)
• Cell Line, Tumor
• Dimerization
• Humans
• Isotope Labeling
• Male
• Metabolic Clearance Rate
• Mice
• Mice, Nude
• Oligopeptides (chemistry, pharmacokinetics)
• Organ Specificity
• Prostatic Neoplasms (diagnostic imaging, metabolism)
• Radionuclide Imaging
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics)
• Tissue Distribution