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Organic & Biomolecular Chemistry
Page 4 of 5
DOI: 10.1039/C8OB01434E
COMMUNICATION
Journal Name
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Y. Seimbille, J. Rousseau, F. Benard, C. Morin, H. Ali, G.
Avvakumov, G. L. Hammond and J. E. van Lier, Steroids,
2002, 67, 765-775.
HPLC purification and their identities were confirmed by mass
spectrometry. [89Zr]Zr-DFO-Cys was successfully conjugated to
c(RGDfK)-CBT (12) in PBS buffer and in presence of TCEP (Fig. S11 in
ESI). Solubility of 12 in aqueous media was limited, and therefore
DMF was used as co-solvent. The final pH of the reaction mixture
was approximately 7.4 and the coupling reaction was carried out at
37 °C for 90 min. We observed that all [89Zr]Zr-DFO-Cys (tR = 13.5
min) was consumed during the reaction and a new signal
corresponding to [89Zr]-5b was visualized at 17.5 min on the HPLC
chromatogram (Fig. S12 in ESI). Similarly, [89Zr]Zr-DFO-CBT was
successfully conjugated to c[RGDyK(C)] (13) in PBS buffer (Fig. S13
in ESI). 13 was freshly prepared to prevent the oxidation of the thiol
moiety and the cycloaddition reaction was performed under the
conditions previously described (Fig. S14 in ESI). More than 98% of
[89Zr]Zr-DFO-CBT (tR = 18.6 min) was consumed during the reaction
and [89Zr]-11b was observed at 16.8 min. We noticed that the time
required for the conjugation of [89Zr]Zr-DFO-Cys or [89Zr]Zr-DFO-CBT
to the corresponding RGD peptide is longer than the time needed
for the coupling with 6-OH-CBT and L-cysteine. Our results are in
accordance with previous data from Jeon et coworkers, who
reported 92% yields in 1 and 20 min for the coupling of their 18F-
labeled CBT-based prosthetic group to cysteine and a dimeric RGD
peptide, respectively.18
A. Orlova, V. Tolmachev, R. Pehrson, M. Lindborg, T. Tran,
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12.
In summary, two novel DFO-based BFCs were developed for
the labeling of biomolecules with zirconium-89 via the
bioorthogonal ligation of 2-cyanobenzothiazole and 1,2-
aminothiol. Both BFCs were easily prepared and labeled at
room temperature with [89Zr]Zr-oxalate. [89Zr]Zr-DFO-Cys and
[89Zr]Zr-DFO-CBT have been rapidly and specifically conjugated
to RGD peptides at 37 °C and pH 7.4. The luciferin linkage
displayed good in vitro stability. Successful labeling of the N-
terminal cysteine residue of 13 with [89Zr]Zr-DFO-CBT indicated
that 10 could also be used for chemoselective 89Zr-labeling of
other cysteine-bearing biomolecules, such as proteins and
antibodies. Moreover, the orthogonality of the reaction, the
metabolic stability of the ligation reagents and the end-
product suggest that the luciferin-adduct formation might be
compatible for pretargeted imaging, provided that reaction
kinetics are favorable.
13.
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S. E. Rudd, P. Roselt, C. Cullinane, R. J. Hicks and P. S.
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Squatrito, J. L. Martinez-Torrecuadrada and F. Mulero,
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J. Jeon, B. Shen, L. Xiong, Z. Miao, K. H. Lee, J. Rao and F.
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pharmaceutics, 2014, 11, 3947-3956.
We gratefully acknowledge the Leenaards Foundation (grant #
3699) and NSERC for financial support. We thank the NMR and MS
facilities in the Chemistry department at the University of British
Columbia for providing support and resources. We would like to
thank the Cyclotron group at the BC Cancer Agency Department of
Functional Imaging for their support on the production of 89Zr and
the Life Sciences team at TRIUMF for technical assistance.
20.
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22.
J. A. H. Inkster, D. J. Colin and Y. Seimbille, EJNMMI
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Laverman, H. Haas, M. Petrik, R. Haubner and C.
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2150.
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Conflicts of Interest
The authors declare that they have no conflict of interest.
Notes and references
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9233.
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4 | J. Name., 2012, 00, 1-3
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