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Convenient Entry to 18F-Labeled Amines through the Staudinger Reduction.

ABSTRACT: Fluorine-18 possesses outstanding decay characteristics for positron emission tomography (PET) imaging. Therefore, it is ideally suited for clinical applications. As such, improved strategies to incorporate fluorine-18 into bioactive molecules are of utmost importance. Indirect 18F-labeling with amino-functionalized synthons is a convenient and versatile approach to synthesize a broad variety of PET tracers. Herein, we report a method to convert 18F-labeled azides to primary amines by means of the Staudinger reduction. Aliphatic and aromatic 18F-labeled azides were converted into the corresponding amines with high conversion yields. The method was easily automated. From a broader perspective, the applied strategy results in two useful synthons from a single precursor and thus increases the flexibility to label diverse chemical scaffolds with minimal synthetic effort.

SUBMITTER: Steen EJL

PROVIDER: S-EPMC6471115 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Convenient Entry to 18F-Labeled Amines through the Staudinger Reduction.

Stéen E Johanna L EJL Shalgunov Vladimir V Denk Christoph C Mikula Hannes H Kjær Andreas A Kristensen Jesper L JL Herth Matthias M MM

European journal of organic chemistry 20190122 8

Fluorine-18 possesses outstanding decay characteristics for positron emission tomography (PET) imaging. Therefore, it is ideally suited for clinical applications. As such, improved strategies to incorporate fluorine-18 into bioactive molecules are of utmost importance. Indirect 18F-labeling with amino-functionalized synthons is a convenient and versatile approach to synthesize a broad variety of PET tracers. Herein, we report a method to convert 18F-labeled azides to primar ...[more]

PMID: 31007573

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Project description:UnlabelledEpidermal growth factor receptor (EGFR) is often overexpressed in a variety of human cancers, and its expression is associated with poor prognosis for many cancer types. However, an accurate technique to noninvasively image EGFR expression in vivo is not available in the clinical setting. In this research, an Affibody analog, anti-EGFR Ac-Cys-Z(EGFR:1907), was successfully site-specifically (18)F-labeled for PET of EGFR expression.MethodsThe prosthetic group N-[2-(4-(18)F-fluorobenzamido) ethyl] maleimide ((18)F-FBEM) was conjugated to Ac-Cys-Z(EGFR:1907) under mild conditions (pH 7) to produce the probe (18)F-FBEM-Cys-Z(EGFR:1907). The binding affinity and specificity tests of (18)F-FBEM-Cys-Z(EGFR:1907) to EGFR were conducted using A431 cancer cells. Small-animal PET and biodistribution studies were conducted on various mice tumor xenograft models with EGFR overexpression (6 types) after injection of approximately 2.0 MBq of (18)F-FBEM-Cys-Z(EGFR:1907) with or without coinjection of unlabeled Ac-Cys-Z(EGFR:1907) for up to 3 h after injection. A correlation study between (18)F-FBEM-Cys-Z(EGFR:1907) small- animal PET quantification and ex vivo Western blot analysis of tumor EGFR expression was conducted in those 6 types of tumor models.Results(18)F-FBEM-Cys-Z(EGFR:1907) binds to EGFR with low nanomolar affinity (37 nM) in A431 cells. (18)F-FBEM-Cys-Z(EGFR:1907) rapidly accumulated in the tumor and cleared from most of the normal organs except the liver and kidneys at 3 h after injection, allowing excellent tumor-to-normal tissue contrast to be obtained. In the A431 tumor xenograft model, coinjection of the PET probe with 45 μg of Ac-Cys-Z(EGFR:1907) was able to improve the tumor uptake (3.9 vs. 8.1 percentage of the injected radioactive dose per gram of tissue, at 3 h after injection) and tumor imaging contrast, whereas coinjection with 500 μg of Ac-Cys-Z(EGFR:1907) successfully blocked the tumor uptake significantly (8.1 vs. 1.0 percentage of the injected radioactive dose per gram of tissue, at 3 h after injection, 88% inhibition, P < 0.05). Moderate correlation was found between the tumor tracer uptake at 3 h after injection quantified by PET and EGFR expression levels measured by Western blot assay (P = 0.007, R = 0.59).Conclusion(18)F-FBEM-Cys-Z(EGFR:1907) is a novel protein scaffold-based PET probe for imaging EGFR overexpression of tumors, and its ability to differentiate tumors with high and low EGFR expression in vivo holds promise for future clinical translation.

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Convenient Entry to 18F-Labeled Amines through the Staudinger Reduction.

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Convenient Entry to <sup>18</sup>F-Labeled Amines through the Staudinger Reduction.

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