Development of the First Aliphatic 18F-Labeled Tetrazine Suitable for Pretargeted PET Imaging-Expanding the Bioorthogonal Tool Box
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Development of the First Aliphatic 18F-Labeled Tetrazine Suitable for Pretargeted PET Imaging-Expanding the Bioorthogonal Tool Box. / Battisti, Umberto M; Bratteby, Klas; Jørgensen, Jesper T; Hvass, Lars; Shalgunov, Vladimir; Mikula, Hannes; Kjær, Andreas; Herth, Matthias Manfred.
I: Journal of Medicinal Chemistry, Bind 64, Nr. 20, 2021, s. 15297–15312.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Development of the First Aliphatic 18F-Labeled Tetrazine Suitable for Pretargeted PET Imaging-Expanding the Bioorthogonal Tool Box
AU - Battisti, Umberto M
AU - Bratteby, Klas
AU - Jørgensen, Jesper T
AU - Hvass, Lars
AU - Shalgunov, Vladimir
AU - Mikula, Hannes
AU - Kjær, Andreas
AU - Herth, Matthias Manfred
PY - 2021
Y1 - 2021
N2 - Pretargeted imaging of nanomedicines have attracted considerable interest because it has the potential to increase imaging contrast while reducing radiation burden to healthy tissue. Currently, the tetrazine ligation is the fastest bioorthogonal reaction for this strategy and, consequently, the state-of-art choice for in vivo chemistry. We have recently identified key properties for tetrazines in pretargeting. We have also developed a method to 18F-label reactive tetrazines using an aliphatic nucleophilic substitution strategy. Here, we combined this knowledge and developed an 18F-labeled tetrazine for pretargeted imaging. In order to develop this ligand, a small SAR study was performed. The most promising compound was selected for labeling and subsequent positron-emission-tomography in vivo imaging. Radiolabeling was achieved in satisfactory yields, molar activities, and high radiochemical purities. [18F]15 displayed favorable pharmacokinetics and remarkable target-to-background ratios-as early as 1 h post injection. We believe that this agent could be a promising candidate for translation into clinical studies.
AB - Pretargeted imaging of nanomedicines have attracted considerable interest because it has the potential to increase imaging contrast while reducing radiation burden to healthy tissue. Currently, the tetrazine ligation is the fastest bioorthogonal reaction for this strategy and, consequently, the state-of-art choice for in vivo chemistry. We have recently identified key properties for tetrazines in pretargeting. We have also developed a method to 18F-label reactive tetrazines using an aliphatic nucleophilic substitution strategy. Here, we combined this knowledge and developed an 18F-labeled tetrazine for pretargeted imaging. In order to develop this ligand, a small SAR study was performed. The most promising compound was selected for labeling and subsequent positron-emission-tomography in vivo imaging. Radiolabeling was achieved in satisfactory yields, molar activities, and high radiochemical purities. [18F]15 displayed favorable pharmacokinetics and remarkable target-to-background ratios-as early as 1 h post injection. We believe that this agent could be a promising candidate for translation into clinical studies.
U2 - 10.1021/acs.jmedchem.1c01326
DO - 10.1021/acs.jmedchem.1c01326
M3 - Journal article
C2 - 34649424
VL - 64
SP - 15297
EP - 15312
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 20
ER -
ID: 282314439