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Improving Tumor‐to‐Background Contrast through Hydrophilic Tetrazines: The Construction of 18 F‐Labeled PET Agents Targeting Nonsmall Cell Lung Carcinoma
Author(s) -
Feng. Huijuan,
Zhang He,
Wang Mengzhe,
Vannam Raghu,
Wang Hui,
Yan Xuefeng,
Ouyang Wei,
Jia Xinqiao,
Fox Joseph M.,
Li Zibo
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202000028
Subject(s) - tetrazine , bioorthogonal chemistry , conjugate , neurotensin , neurotensin receptor , chemistry , combinatorial chemistry , stereochemistry , click chemistry , receptor , biochemistry , organic chemistry , mathematical analysis , mathematics , neuropeptide
Bioorthogonal reactions have been widely used in the biomedical field. 18 F‐TCO/Tetrazine ligation is the most reactive radiolabelled inverse electron demand Diels–Alder reaction, but its application had been limited due to modest contrast ratios of the resulting conjugates. Herein, we describe the use of hydrophilic tetrazines to improve tumor‐to‐background contrast of neurotensin receptor targeted PET agents. PET agents were constructed using a rapid Diels–Alder reaction of the radiolabeled trans ‐cyclooctene ( 18 F‐sTCO) with neurotensin (NT) conjugates of a 3,6‐diaryltetrazine, 3‐methyl‐6‐aryltetrazine, and a derivative of 3,6‐di(2‐hydroxyethyl)tetrazine. Although cell binding assays demonstrated all agents have comparable binding affinity, the conjugate derived from 3,6‐di(2‐hydroxyethyl)tetrazine demonstrated the highest tumor to muscle contrast, followed by conjugates of the 3‐methyl‐6‐aryltetrazine and 3,6‐diaryltetrazine.