@article {Wu1536, author = {Zhanhong Wu and Zi-Bo Li and Kai Chen and Weibo Cai and Lina He and Frederick T. Chin and Fang Li and Xiaoyuan Chen}, title = {microPET of Tumor Integrin αvβ3 Expression Using 18F-Labeled PEGylated Tetrameric RGD Peptide (18F-FPRGD4)}, volume = {48}, number = {9}, pages = {1536--1544}, year = {2007}, doi = {10.2967/jnumed.107.040816}, publisher = {Society of Nuclear Medicine}, abstract = {In vivo imaging of αvβ3 expression has important diagnostic and therapeutic applications. Multimeric cyclic RGD peptides are capable of improving the integrin αvβ3{\textendash}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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/48/9/1536}, eprint = {https://jnm.snmjournals.org/content/48/9/1536.full.pdf}, journal = {Journal of Nuclear Medicine} }