1442
M. Kuchar et al.
one-step 18F-labeling of peptides via nucleophilic aromatic
substitution. Bioconjugate Chem 20:2254–2261
Bejot R, Elizarov AM, Ball E, Zhang J, Miraghaie R, Kolb HC,
Gouverneur V (2011) Batch-mode microfluidic radiosynthesis of
N-succinimidyl-4-[18F]fluorobenzoate for protein labelling.
J Label Compd Radiopharm 54:117–122
radiolabeling of 7 produced predominantly [18F]8 even at
pH 7.
The influence of the chosen conditions on selectivity was
most pronounced for peptide 3 while there was a tendency
for an equal distribution of the radiolabeling products at pH
7/50°C and pH 9/25°C. Theses results show that the out-
come of the radiolabeling reaction is unpredictable for any
peptide and difficult to control by the pH value.
Cai LS, Lu SY, Pike VW (2008) Chemistry with [F-18]fluoride ion.
Eur J Org Chem 17:2853–2873
Chen K, Conti PS (2010) Target-specific delivery of peptide-based
probes for PET imaging. Adv Drug Delivery Rev 62:1005–1022
Chrencik JE, Brooun A, Recht MI, Nicola G, Davis LK, Abagyan R,
Widmer H, Pasquale EB, Kuhn P (2007) Three-dimensional
structure of the EphB2 receptor in complex with an antagonistic
peptide reveals a novel mode of inhibition. J Biol Chem
282:36505–36513
Conclusion
Glaser M, Robins EG (2009) ‘Click-labelling’ in PET-radiochemistry.
J Label Compd Radiopharm 52:407–414
Glaser M, Arstad E, Luthra SK, Robins EG (2009) Two-step
radiosynthesis of [F-18]N-succinimidyl-4-fluorobenzoate ([F-
18]SFB). J Label Compd Radiopharm 52:327–330
Hausner SH, Marik J, Gagnon MKJ, Sutcliffe JL (2008) In vivo
positron emission tomography (PET) imaging with an avb6
specific peptide radiolabeled using 18F-‘‘click’’ chemistry: Eval-
uation and comparison with the corresponding 4-[18F]fluor-
obenzoyl- and 2-[18F]fluoropropionyl-peptides. J Med Chem
51:5901–5904
Helseth DL, Lechner JH, Veis A (1979) Role of the amino-terminal
extra-helical region of type-I collagen in directing the 4D
overlap in fibrillogenesis. Biopolymers 18:3005–3014
Hermanson GT (2008) Bioconjugate techniques, 2nd edn. Academic
Press, Amsterdam
Hoppmann S, Haase C, Richter S, Pietzsch J (2008) Expression,
purification and fluorine-18 radiolabeling of recombinant S100
proteins—potential probes for molecular imaging of receptor for
advanced glycation endproducts (RAGE) in vivo. Protein Expres
Purif 57:143–152
Jacobson O, Zhu L, Ma Y, Weiss ID, Sun X, Niu G, Kiesewetter DO,
Chen X (2011) Rapid and simple one-step F-18 labeling of
peptides. Bioconjugate Chem 22:422–428
Kaiser E, Colescott RL, Bossinger CD, Cook PI (1970) Color test for
detection of free terminal amino groups in the solid-phase
synthesis of peptides. Anal Biochem 34:595–598
Kapty J, Kniess T, Wuest F, Mercer JR (2011) Radiolabeling of
phosphatidylserine-binding peptides with prosthetic groupsN-[6-(4-
[18F]fluorobenzylidene)aminooxyhexyl]maleimide ([18F]FBAM)
and N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). Appl Radiat
Isot 69:1218–1225
In this study a method for the site-selective labeling of
peptides with fluorine-18 on solid support using [18F]SFB,
the most common prosthetic reagent for introduction of
radiofluorine into biomolecules, was developed. Its
advantages over the conventional radiolabeling in solution
could be exemplarily demonstrated by systematic com-
parison of radiolabeling on solid phase and in solution for
four different biologically relevant peptides. The elabo-
rated methodology revealed especially advantageous for
the radiolabeling of peptides containing multiple lysines
such as k7-fragment 5 and can be also applied for labeling
at sites distinct from the N-terminus as exemplarily shown
for SNEW peptide 7. Labeling on solid phase was in each
case more reliable and efficient as a site-selective reaction
with [18F]SFB in aqueous solution revealed as impossible
for every considered peptide despite systematic variation of
pH and temperature. The benefits of the solid-phase
approach become especially obvious if one considers the
time-consuming optimizations that were necessary to sep-
arate the isomeric fluorobenzoylated peptides chromato-
graphically. Labeling with [18F]SFB on solid support has
certainly the potential for straight-forward introduction of
fluorine-18 into almost every peptide that is interesting as
imaging probe for PET.
Acknowledgments The dedicated assistance of Uta Lenkeit and
Peggy Wecke in the radiosynthesis of [18F]SFB is gratefully
acknowledged.
King DS, Fields CG, Fields GB (1990) A cleavage method which
minimizes side reactions following Fmoc solid-phase peptide
synthesis. Int J Peptide Protein Res 36:255–266
Koolpe M, Burgess R, Dail M, Pasquale EB (2005) EphB receptor-
binding peptides identified by phage display enable design of an
Conflict of interest The authors declare that they have no conflict
of interest.
antagonist with ephrin-like affinity.
280:17301–17311
J
Biol Chem
Kuhnast B, Dolle F (2010) The challenge of labeling macromolecules
with fluorine-18: Three decades of research. Curr Radiopharm
3:174–201
Li Z, Conti PS (2010) Radiopharmaceutical chemistry for positron
emission tomography. Adv Drug Delivery Rev 62:1031–1051
References
Barry GD, Le GT, Fairlie DP (2006) Agonists and antagonists of
protease activated receptors (PARs). Curr Med Chem
13:243–265
¨
¨
¨
Mading P, Fuchtner F, Wust F (2005) Module-assisted synthesis of
the bifunctional labelling agent N-succinimidyl 4-[F-18]fluor-
obenzoate ([F-18]SFB). Appl Radiat Isot 63:329–332
Becaud J, Mu L, Karramkam M, Schubiger PA, Ametamey SM,
Graham K, Stellfeld T, Lehmann L, Borkowski S, Berndorff D,
Dinkelborg L, Srinivasan A, Smits R, Koksch B (2009) Direct
Mamat C, Ramenda T, Wuest FR (2009) Recent applications of click
chemistry for the synthesis of radiotracers for molecular
imaging. Mini-Rev Org Chem 6:21–34
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