TY - JOUR

T1 - [11C]Carboxylated Tetrazines for Facile Labeling of Trans-Cyclooctene-Functionalized PeptoBrushes

AU - García-Vázquez, Rocío

AU - Battisti, Umberto Maria

AU - Shalgunov, Vladimir

AU - Schäfer, Gabriela

AU - Barz, Matthias

AU - Herth, Matthias Manfred

N1 - Funding Information: This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska‐Curie grant agreement no. 813528. M.M.H. has received funding from the European Union's EU Framework Programme for Research and Innovation Horizon 2020 (grant agreement no. 670261). V.S. was supported by BRIDGE – Translational Excellence Programme at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant agreement no. NNF18SA0034956).

PY - 2022

Y1 - 2022

N2 - Functionalization of macromolecules (antibodies, polymers, nanoparticles) with click-reactive groups greatly enhances the versatility of their potential applications. Click chemistry based on tetrazine – trans-cyclooctene (TCO) ligation is especially promising and is already widely applied for pretargeted imaging and therapy. Indirect radiolabeling of TCO-functionalized macromolecules with substoichiometric amounts of radioactive tetrazines is a convenient way to monitor the fate of those macromolecules by means of positron emission tomography (PET) imaging after their administration into the test subject. In this work, the preparation is reported of TCO-containing graft copolymers, namely PeptoBrushes (polyglutamic acid-graft-polysarcosine), novel [11C]carboxylated tetrazines, and their combined use in radiolabeling the polymer by inverse electron demand Diels Alder reaction, to investigate it is potential for an application in pretarget imaging or injectable brachytherapy. The procedure for [11C]tetrazine production is easy and scalable, while indirect TCO-PeptoBrushes labeling with these [11C]tetrazines is mild, fast, and quantitative. This strategy allows facile 11C-labeling of diverse TCO-functionalized macromolecules, so that their localization and distribution shortly after injection can be assessed by PET.

AB - Functionalization of macromolecules (antibodies, polymers, nanoparticles) with click-reactive groups greatly enhances the versatility of their potential applications. Click chemistry based on tetrazine – trans-cyclooctene (TCO) ligation is especially promising and is already widely applied for pretargeted imaging and therapy. Indirect radiolabeling of TCO-functionalized macromolecules with substoichiometric amounts of radioactive tetrazines is a convenient way to monitor the fate of those macromolecules by means of positron emission tomography (PET) imaging after their administration into the test subject. In this work, the preparation is reported of TCO-containing graft copolymers, namely PeptoBrushes (polyglutamic acid-graft-polysarcosine), novel [11C]carboxylated tetrazines, and their combined use in radiolabeling the polymer by inverse electron demand Diels Alder reaction, to investigate it is potential for an application in pretarget imaging or injectable brachytherapy. The procedure for [11C]tetrazine production is easy and scalable, while indirect TCO-PeptoBrushes labeling with these [11C]tetrazines is mild, fast, and quantitative. This strategy allows facile 11C-labeling of diverse TCO-functionalized macromolecules, so that their localization and distribution shortly after injection can be assessed by PET.

U2 - 10.1002/marc.202100655

DO - 10.1002/marc.202100655

M3 - Journal article

C2 - 34888977

AN - SCOPUS:85122038882

VL - 43

JO - Macromolecular Rapid Communications

JF - Macromolecular Rapid Communications

SN - 1022-1336

IS - 12

M1 - 2100655

ER -