RT Journal Article
SR Electronic
T1 Conformationally strained trans-cyclooctene (sTCO) enables the rapid construction of 18F-PET probes via tetrazine ligation
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1096
OP 1096
VO 57
IS supplement 2
A1 Wang, Mengzhe
A1 Svatunek, Dennis
A1 Rohlfing, Katarina
A1 Liu, Yu
A1 Wang, Hui
A1 Giglio, Benjamin
A1 Yuan, Hong
A1 Wu, Zhanhong
A1 Fox, Joseph
A1 Li, Zibo
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/1096.abstract
AB 1096Objectives There is a high demand for new methods that efficiently introduce 18F to biological macromolecules for PET imaging applications. Here we describe 18F-sTCO, a new radiotracer based on the most reactive trans-cyclooctene dienophile described to date. This highly reactive radiotracer is used for the rapid construction of 18F-PET probes through tetrazine ligation.Methods Starting from the tosylated precursor, an 18F labeled sTCO derivative was synthesized. The reaction rate constant of sTCO and an a diphenyl-s-tetrazine was measured by stopped flow kinetic analysis. A cyclic RGD-tetrazine conjugate was prepared from 18F-sTCO and the resulting imaging probe was subjected to in vitro stability and micro PET studies in human U87MG tumor bearing mice.Results sTCO can be labeled with an isolation yield of 9.3+/- 2.4% with high specific activity. Extremely fast reactivity (up to 2.86 x 105 M-1s-1 in water at rt) was observed in the reaction of sTCO and tetrazine derivatives. The 18F-sTCO-Tetrazine-RGD probe demonstrated prominent and persistent tumor uptake in vivo with good tumor to background contrast.Conclusions A conformationally strained trans-cyclooctene, 18F-sTCO, was developed and shown to have extremely fast reaction rate in tetrazine ligation. The constructed PET probe demonstrated specific tumor uptake and good tumor to background contrast.