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RESEARCH PRODUCT
Improved radiosynthesis and preliminary in vivo evaluation of the 11C-labeled tetrazine [11C]AE-1 for pretargeted PET imaging
Kamilla NorregaardJohn F. ValliantPatricia E. EdemVladimir ShalgunovAbdolreza YazdaniHanne D. HansenAndreas KjaerAlexander BirkeSzabolcs LehelIda Nymann PetersenElina T. L’estradeTomas OhlssonJesper L. KristensenGitte M. KnudsenJonas VilladsenMatthias BarzE. Johanna L. StéenJesper Tranekjær JørgensenMatthias M. HerthMaria Erlandssonsubject
Nuclear imagingClinical BiochemistryTetrazinePET imagingPharmaceutical ScienceCarbon-1101 natural sciencesBiochemistryTetrazinechemistry.chemical_compoundIn vivoTrans-cycloocteneDrug DiscoveryMolecular BiologyPretargetingPretargeting010405 organic chemistryChemistryOrganic ChemistryRadiosynthesisPet imaging3. Good health0104 chemical sciences010404 medicinal & biomolecular chemistryMolecular MedicineBiomedical engineeringdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-04-01 | Bioorganic & Medicinal Chemistry Letters |