Protein labeling with the labeling precursor [18f]sifa-sh for positron emission tomography

ABSTRACT Proteins previously derivatized with the cross-coupling reagent sulfo-SMCC (4-(_N_-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-_N_-hydroxy-succinimide ester sodium salt)

can be easily labeled in high radiochemical yields with the silicon-fluoride acceptor (SiFA) reagent [18F]SiFA-SH, obtained via isotopic exchange, by thiol-maleimide coupling chemistry (_n_

= 10). The specific activity of SiFA-SH obtained in a one-step labeling reaction was >18.5 GBq μmol−1 (>500 Ci mmol−1). The number of SiFA building blocks per protein molecule is

defined by the previously introduced number of maleimide groups, which can be determined by a simple and convenient Ellman's assay. Not more than two maleimide groups are introduced

using sulfo-SMCC, thereby keeping the modification of the protein low and preserving its biological activity. Access through your institution Buy or subscribe This is a preview of

subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year only

$21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout

ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS [18F]DIFLUOROCARBENE FOR

POSITRON EMISSION TOMOGRAPHY Article 28 March 2022 EXPANDING TRACER SPACE FOR POSITRON EMISSION TOMOGRAPHY WITH HIGH MOLAR ACTIVITY 18F-LABELED Α,Α-DIFLUOROMETHYLALKANES Article Open access

13 February 2025 DEOXYFLUORINATION OF PHENOLS FOR CHEMOSELECTIVE 18F-LABELING OF PEPTIDES Article 18 October 2023 CHANGE HISTORY * _ 23 OCTOBER 2012  In the version of this article initially

published online, Katy Orchowski's name was spelled incorrectly. The surname Orchovski has been corrected to read Orchowski. The error has been corrected in all versions of this

article. _ REFERENCES * Kostikov, A.P. et al. Synthesis of [18F]SiFB: a prosthetic group for direct protein radiolabeling for application in positron emission tomography. _Nat. Protoc._ 7,

1956–1963 (2012). Article  CAS  Google Scholar  * Wängler, C. et al. One-step 18F-labeling of peptides for positron emission tomography imaging using the SiFA methodology. _Nat. Protoc._ 7,

1946–1955 (2012). Article  Google Scholar  * Wängler, C. et al. Protein based imaging agents for _in vivo_ positron-emission-tomography: a universally applicable gallium-68 labeling

technique. _J. Nucl. Med._ 52, 586–591 (2011). Article  Google Scholar  * Ting, R., Adam, M.J., Ruth, T.J. & Perrin, D.M. Arylfluoroborates and alkylfluorosilicates as potential PET

imaging agents: high-yielding aqueous biomolecular F-18-labeling. _J. Am. Chem. Soc._ 127, 13094–13095 (2005). Article  CAS  Google Scholar  * Li, Y. et al. Towards kit-like 18F-labeling of

marimastat, a noncovalent inhibitor drug for _in vivo_ PET imaging cancer associated matrix metalloproteases. _Med. Chem. Commun._ 2, 942–949 (2011). Article  CAS  Google Scholar  * Ting, R.

et al. Toward [18F]-labeled aryltrifluoroborate radiotracers: _in vivo_ positron emission tomography imaging of stable aryltrifluoroborate clearance in mice. _J. Am. Chem. Soc._ 130,

12045–12055 (2008). Article  CAS  Google Scholar  * McBride, W.J. et al. A novel method of 18F radiolabeling for PET. _J. Nucl. Med._ 50, 991–998 (2009). Article  CAS  Google Scholar  *

McBride, W.J. et al. Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex. _Bioconjug. Chem._ 21, 1331–1340 (2010). Article  CAS  Google Scholar  * McBride, W.J.,

D'Souza, C.A., Sharkey, R.M. & Goldenberg, D.M. The radiolabeling of proteins by the [18F]AlF method. _Appl. Radiat. Isot._ 70, 200–204 (2012). Article  CAS  Google Scholar  * Cai,

L., Lu, S. & Pike, V.W. Chemistry with [18F]fluoride ion. _Eur. J. Org. Chem._ 2008, 2853–2873 (2008). Article  Google Scholar  * Smith, G.E., Sladen, H.L., Biagini, C.G. & Blower,

P.J. Inorganic approaches for radiolabeling biomolecules with fluorine-18 for imaging with positron emission tomography. _Dalton Trans._ 40, 6196–6205 (2001). Article  Google Scholar  * Wu,

Z. & Kandeel, F. 18F-labeled proteins. _Curr. Pharm. Biotechnol._ 11, 572–580 (2010). Article  CAS  Google Scholar  * Wester, H.J. & Schottelius, M. Fluorine-18 labeling of peptides

and proteins. _Ernst Schering Res. Found. Workshop_ 62, 79–111 (2007). Article  CAS  Google Scholar  * Vaidyanathan, G. & Zalutsky, M.R. Labeling proteins with fluorine-18 using

_N_-succinimidyl 4-[18F]fluorobenzoate. _Nucl. Med. Biol._ 19, 275–281 (1992). CAS  Google Scholar  * Brikh, A. & Morin, C. Boronated thiophenols: a preparation of

4-mercaptophenylboronic acid and derivatives. _J. Organomet. Chem._ 581, 82–86 (1999). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the cyclotron crew of the

McConnell Brain Imaging Centre for providing fluorine-18. The financial support of the following grant agencies are gratefully acknowledged: Canada Foundation for Innovation project no.

203639 to R.S., Natural Sciences and Engineering Research Council of Canada (NSERC) Strategic Project Grant Program (STPGP) no. 412893 to R.S., Bayern-Quebec-Allianz to S.N., Deutsche

Forschungsgemeinschaft (DFG) grant no. WA 2132/3-1 to B.W. and Fonds der Chemischen Industrie to C.W. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Clinical Radiology and

Nuclear Medicine, Molecular Imaging and Radiochemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Björn Wängler & Sabrina Niedermoser * McConnell Brain Imaging

Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada Alexey P Kostikov, Joshua Chin, Katy Orchowski, Esther Schirrmacher & Ralf Schirrmacher * Department

of Nuclear Medicine, Hospital of the Ludwig-Maximilians-University, Munich, Germany Sabrina Niedermoser & Carmen Wängler * Lehrstuhl für Anorganische Chemie II, Technische Universität

Dortmund, Dortmund, Germany Liuba Iovkova-Berends & Klaus Jurkschat * Biomedical Chemistry, Medical Faculty Mannheim, Medical Research Center Mannheim, Heidelberg University, Mannheim,

Germany Carmen Wängler Authors * Björn Wängler View author publications You can also search for this author inPubMed Google Scholar * Alexey P Kostikov View author publications You can also

search for this author inPubMed Google Scholar * Sabrina Niedermoser View author publications You can also search for this author inPubMed Google Scholar * Joshua Chin View author

publications You can also search for this author inPubMed Google Scholar * Katy Orchowski View author publications You can also search for this author inPubMed Google Scholar * Esther

Schirrmacher View author publications You can also search for this author inPubMed Google Scholar * Liuba Iovkova-Berends View author publications You can also search for this author

inPubMed Google Scholar * Klaus Jurkschat View author publications You can also search for this author inPubMed Google Scholar * Carmen Wängler View author publications You can also search

for this author inPubMed Google Scholar * Ralf Schirrmacher View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS A.P.K., S.N., J.C., K.O., E.S.,

L.I.-B., K.J. and C.W. performed the experimental work. R.S., C.W. and B.W. wrote the manuscript. CORRESPONDING AUTHORS Correspondence to Carmen Wängler or Ralf Schirrmacher. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Wängler, B.,

Kostikov, A., Niedermoser, S. _et al._ Protein labeling with the labeling precursor [18F]SiFA-SH for positron emission tomography. _Nat Protoc_ 7, 1964–1969 (2012).

https://doi.org/10.1038/nprot.2012.111 Download citation * Published: 04 October 2012 * Issue Date: November 2012 * DOI: https://doi.org/10.1038/nprot.2012.111 SHARE THIS ARTICLE Anyone you

share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the

Springer Nature SharedIt content-sharing initiative