Stability of fluorotrialkylsilanes as prosthetic groups for instant labelling of biomolecules with fluorine-18

Choudhry, Uzma, Martin, K., Mainard, D., Biagini, Stefano C. G., Blower, Philip J. (2006) Stability of fluorotrialkylsilanes as prosthetic groups for instant labelling of biomolecules with fluorine-18. European Journal of Nuclear Medicine and Molecular Imaging, 33 (S2). p. 306. ISSN 0340-6997. (doi:10.1007/s00259-006-0217-0) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1007/s00259-006-0217-0

Abstract

Background: Current methods for 18F labelling of peptides for PET imaging are time-consuming and complex. More efficient (preferably single step) methods, analogous to 99mTc kits, are required because of the short half-life (110 min) of 18F. It has been suggested [1] that single-step nucleophilic fluorination with fluoride ions may be possible using silicon-fluorine chemistry. Aims: This work aims to identify suitable alkyl groups to include in the required alkoxytrialkylsilane, in order to achieve the fastest radiolabelling nucleophilic displacement of alkoxide by fluoride) and optimal kinetic stability of the Si-F bond (and hence optimal in vivo stability). Material & Methods: Four model trialkylfluorosilanes were synthesised and evaluated using HPLC and NMR to determine rates of formation and hydrolysis of Si-F bonds: ButPh2SiF, Ph3SiF, ButMe2SiF, and Me2PhSiF. The fluorosilanes were incubated in 1:1 phosphate buffered saline (pH 7.4):acetonitrile solution, and in 1:1 acetate buffer (pH 5):acetonitrile, 1:1 bicarbonate buffer (pH 8.5 and 11). Results: Rapid Si-F bond formation (within 5 minutes at 40oC) on reaction of trialkylalkoxysilanes with fluoride was confirmed by NMR and HPLC in all cases, showing that rapid fluorination is feasible. However, only ButPh2SiF showed sufficient hydrolytic stability at 40oC to allow feasibility of imaging studies. At pHs 5 and 7.5 hydrolysis of ButPh2SiF was not detectable even at 6 h. In alkaline conditions its hydrolysis was more rapid: at pH 8.5 it was below 15% at 2 h, and at pH 11 it was complete before 1.75 h. Conclusion: The hydrolysis of the Si-F bond to give a hydroxysilane and fluoride is base-catalysed but is slow at acidic, neutral and mildly basic pH. The rate of Si-F bond formation from alkoxysilane is fast enough for radiolabelling within a few minutes. Steric hindrance is a requirement to ensure adequate kinetic stability of the Si-F bond, and the t-butyldiphenylalkoxysilane group has therefore been selected for further development as a prosthetic group for single step labeling with 18F- ions straight from the cyclotron.

Item Type: Article
DOI/Identification number: 10.1007/s00259-006-0217-0
Subjects: Q Science
Q Science > QD Chemistry
Divisions: Faculties > Sciences > School of Physical Sciences > Functional Materials Group
Faculties > Sciences > School of Physical Sciences
Depositing User: Stefano C G Biagini
Date Deposited: 16 Mar 2009 16:53 UTC
Last Modified: 11 Jun 2019 14:10 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/13247 (The current URI for this page, for reference purposes)
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