RT Journal Article SR Electronic T1 18F labeling of cysteine containing peptides (RGD and Exendin-4) and protein (VEGF) with high yield and specific activity using tetrazine-trans-cyclooctene ligation JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 188 OP 188 VO 53 IS supplement 1 A1 Shuanglong Liu A1 Matthew Hassink A1 Zhanhong Wu A1 Ramajeyam Selvaraj A1 Hui Wang A1 Xiaoyuan Chen A1 Fouad Kandeel A1 Joseph Fox A1 Zibo Li A1 Peter Conti YR 2012 UL http://jnm.snmjournals.org/content/53/supplement_1/188.abstract AB 188 Objectives The tetrazine-trans-cyclooctene ligation has been developed as a novel 18F labeling method that proceeds with fast reaction rates without catalysis. The aim of this study was to develop an efficient method for 18F-lableing of free cysteines of peptide and protein based on sequential ligation with a bifunctional tetrazinyl-maleimide and an 18F-labeled trans-cyclooctene. Methods The newly developed method was tested for site-specific labeling of c(RGDyC), Exendin-4-SH, and VEGF-SH protein. The resulting 18F probes were tested in U87MG glioblastoma model, insulinoma mouse model, and normal nude mice. Results Starting with 4 mCi of 18F-trans-cyclooctene and only 10 μg of tetrazine-RGD (80-100 µM), 5µg of Exendin-4-SH (10µM), or 15 μg of tetrazine-VEGF (6.0 µM), 18F labeled RGD peptide (18F-TTM-RGD), Exendin-4 peptide (18F-TTM-Exendin-4) and VEGF protein (18F-TTM-VEGF) could be obtained within five minutes in 95%, 80%, and 75% yield, respectively. The specific activity of 18F-TTM-RGD was estimated to be approximately 3-6 Ci/µmol. The tumor uptake of 18F-TTM-RGD in U87MG tumor reached 1.98 ± 0.33, 1.80 ± 0.15, and 1.27 ± 0.33 % ID/g at 0.5, 1, and 2 h p.i., respectively. 18F-TTM-VEGF was mainly accumulated in kidneys, which correlated well with previous report. Conclusions A highly efficient method has been developed for site-specific 18F labeling of cysteine containing peptides and proteins. The special characteristics of the tetrazine-trans-cyclooctene ligation provide unprecedented opportunities to synthesize 18F-labeled probes with high specific activity for PET applications