Design, Synthesis, and Evaluation of a Low-Molecular-Weight (11)C-Labeled Tetrazine for Pretargeted PET Imaging Applying Bioorthogonal in Vivo Click Chemistry.
A low-molecular-weight tetrazine labeled with the short-lived positron emitter carbon-11 was developed as a bioorthogonal PET probe for pretargeted imaging. A method for efficient and fast synthesis of this imaging agent is presented using radiolabeling of a readily available precursor. High reactivity with trans-cyclooctenes was observed and in vivo investigations including PET/MR scanning showed homogeneous biodistribution, good metabolic stability, and rapid excretion in naive mice. These properties are key to the success of bioorthogonal (11)C-PET imaging, which has been shown in a simple pretargeting experiment using TCO-modified mesoporous silica nanoparticles. Overall, this (11)C-labeled tetrazine represents a highly versatile and advantageous chemical tool for bioorthogonal PET imaging and enables pretargeting approaches using carbon-11 for the first time.
Institute of Applied Synthetic Chemistry, Vienna University of Technology , 1040 Wien, Austria.
Christoph
C
Denk
Institute of Applied Synthetic Chemistry, Vienna University of Technology , 1040 Wien, Austria.
Dennis
D
Svatunek
Health and Environment Department, Biomedical Systems, Austrian Institute of Technology , 2444 Seibersdorf, Austria.
Severin
S
Mairinger
Health and Environment Department, Biomedical Systems, Austrian Institute of Technology , 2444 Seibersdorf, Austria.
Johann
J
Stanek
Health and Environment Department, Biomedical Systems, Austrian Institute of Technology , 2444 Seibersdorf, Austria.
Thomas
T
Filip
Institute of Applied Synthetic Chemistry, Vienna University of Technology , 1040 Wien, Austria.
Dominik
D
Matscheko
Health and Environment Department, Biomedical Systems, Austrian Institute of Technology , 2444 Seibersdorf, Austria.
Claudia
C
Kuntner
Health and Environment Department, Biomedical Systems, Austrian Institute of Technology , 2444 Seibersdorf, Austria.
Thomas
T
Wanek
Institute of Applied Synthetic Chemistry, Vienna University of Technology , 1040 Wien, Austria.
Hannes
H
Mikula
D000818:Animals; D002250:Carbon Radioisotopes; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry; D015195:Drug Design; D005260:Female; D007553:Isotope Labeling; D051379:Mice; D008970:Molecular Weight; D049268:Positron-Emission Tomography / Q000379:methods*; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D013777:Tetrazoles