RT Journal Article SR Electronic T1 microPET of Tumor Integrin αvβ3 Expression Using 18F-Labeled PEGylated Tetrameric RGD Peptide (18F-FPRGD4) JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1536 OP 1544 DO 10.2967/jnumed.107.040816 VO 48 IS 9 A1 Zhanhong Wu A1 Zi-Bo Li A1 Kai Chen A1 Weibo Cai A1 Lina He A1 Frederick T. Chin A1 Fang Li A1 Xiaoyuan Chen YR 2007 UL http://jnm.snmjournals.org/content/48/9/1536.abstract AB In vivo imaging of αvβ3 expression has important diagnostic and therapeutic applications. Multimeric cyclic RGD peptides are capable of improving the integrin αvβ3–binding affinity due to the polyvalency effect. Here we report an example of 18F-labeled tetrameric RGD peptide for PET of αvβ3 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 α-amino group. NH2-mini-PEG-E{E[c(RGDyK)]2}2 (PRGD4) was labeled with 18F via the N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) prosthetic group. The receptor-binding characteristics of the tetrameric RGD peptide tracer 18F-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 18F-FPRGD4 was about 15%, with a total reaction time of 180 min starting from 18F-F−. The PEGylation had minimal effect on integrin-binding affinity of the RGD peptide. 18F-FPRGD4 has significantly higher tumor uptake compared with monomeric and dimeric RGD peptide tracer analogs. The receptor specificity of 18F-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 18F-FPRGD4 possessing high integrin-binding affinity and favorable biokinetics is a promising tracer for PET of integrin αvβ3 expression in cancer and other angiogenesis related diseases.