Improved radiosynthesis and preliminary in vivo evaluation of the 11 C-labeled tetrazine [ 11 C]AE-1 for pretargeted PET imaging

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E. Johanna L. Stéen, Jesper T. Jørgensen, Ida N. Petersen, Kamilla Nørregaard, Szabolcs Lehel, Vladimir Shalgunov, Alexander Birke, Patricia E. Edem, Elina T. L'Estrade, Hanne D. Hansen, Jonas Villadsen, Maria Erlandsson, Tomas Ohlsson, Abdolreza Yazdani, John F. Valliant, Jesper L. Kristensen, Matthias Barz, Gitte M. Knudsen, Andreas Kjær, Matthias M. Herth

Pretargeted nuclear imaging based on the ligation between tetrazines and nano-sized targeting agents functionalized with trans-cyclooctene (TCO) has recently been shown to improve both imaging contrast and dosimetry in nuclear imaging of nanomedicines. Herein, we describe the improved radiosynthesis of a 11 C-labeled tetrazine ([ 11 C]AE-1) and its preliminary evaluation in both mice and pigs. Pretargeted imaging in mice was carried out using both a new TCO-functionalized polyglutamic acid and a previously reported TCO-functionalized bisphosphonate system as targeting agents. Unfortunately, pretargeted imaging was not successful using these targeting agents in pair with [ 11 C]AE-1. However, brain imaging in pig indicated that the tracer crossed the blood-brain-barrier. Hence, we suggest that this tetrazine scaffold could be used as a starting point for the development of pretargeted brain imaging, which has so far been a challenging task.

TidsskriftBioorganic and Medicinal Chemistry Letters
StatusUdgivet - 1 jan. 2019

ID: 214297865