microPET of tumor integrin alphavbeta3 expression using 18F-labeled PEGylated tetrameric RGD peptide (18F-FPRGD4).

Abstract

UNLABELLED:

In vivo imaging of alpha(v)beta(3) expression has important diagnostic and therapeutic applications. Multimeric cyclic RGD peptides are capable of improving the integrin alpha(v)beta(3)-binding affinity due to the polyvalency effect. Here we report an example of (18)F-labeled tetrameric RGD peptide for PET of alpha(v)beta(3) expression in both xenograft and spontaneous tumor models.

METHODS:

The tetrameric RGD peptide E{E[c(RGDyK)](2)}(2) was derived with amino-3,6,9-trioxaundecanoic acid (mini-PEG; PEG is poly(ethylene glycol)) linker through the glutamate alpha-amino group. NH(2)-mini-PEG-E{E[c(RGDyK)](2)}(2) (PRGD4) was labeled with (18)F via the N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB) prosthetic group. The receptor-binding characteristics of the tetrameric RGD peptide tracer (18)F-FPRGD4 were evaluated in vitro by a cell-binding assay and in vivo by quantitative microPET imaging studies.

RESULTS:

The decay-corrected radiochemical yield for (18)F-FPRGD4 was about 15%, with a total reaction time of 180 min starting from (18)F-F(-). The PEGylation had minimal effect on integrin-binding affinity of the RGD peptide. (18)F-FPRGD4 has significantly higher tumor uptake compared with monomeric and dimeric RGD peptide tracer analogs. The receptor specificity of (18)F-FPRGD4 in vivo was confirmed by effective blocking of the uptake in both tumors and normal organs or tissues with excess c(RGDyK).

CONCLUSION:

The tetrameric RGD peptide tracer (18)F-FPRGD4 possessing high integrin-binding affinity and favorable biokinetics is a promising tracer for PET of integrin alpha(v)beta(3) expression in cancer and other angiogenesis related diseases.

• Authors: Zhanhong Wu, Zi-Bo Li, Kai Chen, Weibo Cai, Lina He, Frederick T Chin, Fang Li, Xiaoyuan Chen
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 48 Issue 9 Pg. 1536-44 (Sep 2007) ISSN: 0161-5505 [Print] United States
• PMID: 17704249 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Fluorine Radioisotopes
• Integrin alphaVbeta3
• Oligopeptides
• Polyethylene Glycols
• arginyl-glycyl-aspartic acid

Topics

• Animals
• Cell Line, Tumor
• Female
• Fluorine Radioisotopes (pharmacokinetics)
• Humans
• Integrin alphaVbeta3 (biosynthesis)
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Oligopeptides (chemistry, pharmacokinetics)
• Polyethylene Glycols (chemistry)
• Positron-Emission Tomography (methods)
• Transplantation, Heterologous