Issue 12, 2015

A novel 2-cyanobenzothiazole-based 18F prosthetic group for conjugation to 1,2-aminothiol-bearing targeting vectors

Abstract

In a bid to find an efficient means to radiolabel biomolecules under mild conditions for PET imaging, a bifunctional 18F prosthetic molecule has been developed. The compound, dubbed [18F]FPyPEGCBT, consists of a 2-substituted pyridine moiety for [18F]F incorporation and a 2-cyanobenzothiazole moiety for coupling to terminal cysteine residues. The two functionalities are separated by a mini-PEG chain. [18F]FPyPEGCBT could be prepared from its corresponding 2-trimethylammonium triflate precursor (100 °C, 15 min, MeCN) in preparative yields of 11% ± 2 (decay corrected, n = 3) after HPLC purification. However, because the primary radiochemical impurity of the fluorination reaction will not interact with 1,2-aminothiol functionalities, the 18F prosthetic could be prepared for bioconjugation reactions by way of partial purification on a molecularly imprinted polymer solid-phase extraction cartridge. [18F]FPyPEGCBT was used to 18F-label a cyclo-(RGDfK) analogue which was modified with a terminal cysteine residue (TCEP·HCl, DIPEA, 30 min, 43 °C, DMF). Final decay-corrected yields of 18F peptide were 7% ± 1 (n = 9) from end-of-bombardment. This novel integrin-imaging agent is currently being studied in murine models of cancer. We argue that [18F]FPyPEGCBT holds significant promise owing to its straightforward preparation, ‘click’-like ease of use, and hydrophilic character. Indeed, the water-tolerant radio-bioconjugation protocol reported herein requires only one HPLC step for 18F peptide purification and can be carried out remotely using a single automated synthesis unit over 124–132 min.

Graphical abstract: A novel 2-cyanobenzothiazole-based 18F prosthetic group for conjugation to 1,2-aminothiol-bearing targeting vectors

Supplementary files

Article information

Article type
Paper
Submitted
19 Dec 2014
Accepted
03 Feb 2015
First published
13 Feb 2015

Org. Biomol. Chem., 2015,13, 3667-3676

Author version available

A novel 2-cyanobenzothiazole-based 18F prosthetic group for conjugation to 1,2-aminothiol-bearing targeting vectors

J. A. H. Inkster, D. J. Colin and Y. Seimbille, Org. Biomol. Chem., 2015, 13, 3667 DOI: 10.1039/C4OB02637C

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