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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Steen, E. Johanna L.^1,2  Jorgensen, Jesper T.^2,3  Petersen, Ida N.^2,3  Norregaard, Kamilla^2,3  Lehel, Szabolcs²  Shalgunov, Vladimir¹  Birke, Alexander⁴  Edem, Patricia E.^1,2,3  L'Estrade, Elina T.^1,2,5,6,7  Hansen, Hanne D.^5,6  Villadsen, Jonas^5,6  Erlandsson, Maria⁷  Ohlsson, Tomas⁷  Yazdani, Abdolreza⁸  Valliant, John F.⁸  Kristensen, Jesper L.¹  Barz, Matthias⁴  Knudsen, Gitte M.^5,6  Kjaer, Andreas^2,3  Herth, Matthias M.^1,2 

[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark

[2] Univ Hosp Copenhagen, Rigshosp, Dept Clin Physiol Nucl Med & PET, Blegdamsvej 9, DK-2100 Copenhagen, Denmark

[3] Univ Copenhagen, Dept Biomed Sci, Cluster Mol Imaging, Blegdamsvej 3, DK-2200 Copenhagen, Denmark

[4] Johannes Gutenberg Univ Mainz, Inst Organ Chem, Duesbergweg 10-14, D-55099 Mainz, Germany

[5] Rigshosp, Neurobiol Res Unit, Blegdamsvej 9, DK-2100 Copenhagen, Denmark

[6] Univ Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark

[7] Skanes Univ Hosp, Nucl Med Phys Unit, Radiat Phys, Barngatan 3, S-22242 Lund, Sweden

[8] McMaster Univ, Dept Chem & Chem Biol, 1280 Main St West, Hamilton, ON L8S 4M1, Canada

关键词: PET imaging;    Pretargeting;    Carbon-11;    Tetrazine;    Trans-cyclooctene;   

DOI  :  10.1016/j.bmcl.2019.02.014

来源: Elsevier

【 摘 要 】

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 C-11-labeled tetrazine ([C-11]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 [C-11]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.

【 授权许可】

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