obtained by these bioorthogonal click conjugation reactions under physiologically
friendly reaction conditions (such as room temperature, pH 7 and water solvent) to
avoid the decomposition and denaturation of these bio-molecules. In addition, the
18 F labeling procedure became simple for easy handling. In 2011, Weissleder et al.
firstly reported a chemically orthogonal scavenger-assisted high-performance
18 F
labeling protocol using the inverse electron-demand Diels-Alder cycloaddition
reactions to synthesize
18 F labeled PARP1 inhibitor derivative (Fig. 14.6a) [46].
Using this protocol,
18 F labeled PARP1 inhibitor was prepared from the
tetrazine-tethered precursor in 59.6% RCY within 3 min, by the bioorthogonal
tetrazine-trans-cyclooctene ligation reaction with an
18 F labeled TCO synthon.
Moreover, the excess non-labeled tetrazine-tethered precursor could be removed
using a magnetic TCO scavenger resin and they could increase its molar activity. In
2012, it was reported that the bioorthogonal SPAAC based
18 F peptide labeling
reaction could provide various
18 F labeled peptide tracers under physiologicallyfriendly reaction conditions without HPLC purification process. According to this
protocol, the SPAAC reaction of ADIBO-tethered cRGD peptide was reacted with
the
18 F labeled azide synthon in aqueous media and reaction completed within
15 min to afford an
18 F-labeled cRGD peptide quantitatively [47]. Based on
chemically orthogonal scavenger-assisted purification-concept above mentioned, a
subsequent treatment of the mixture solution with the polystyrene-supported azide
scavenger resin for 20 min could allow remove the excess cold ADIBO–cRGD
precursors (Fig. 14.6b). Just after filtration and washing using a PBS, the
18 F
labeled cRGD peptide could be synthesized in a 92% RCY within the total reaction
time of 35 min. What is more appealing was that this RGD radiotracer was obtained
Fig. 14.5 Concept of the molar activity of radiolabeled molecular imaging probes for targeting.
a Low molar activity of radiotracer: bad image quality with high toxicity. b High molar activity of
radiotracer: good image quality with low toxicity
14 Bioorthogonal Reaction for Fluorine-18 Labeling
269
friendly reaction conditions (such as room temperature, pH 7 and water solvent) to
avoid the decomposition and denaturation of these bio-molecules. In addition, the
18 F labeling procedure became simple for easy handling. In 2011, Weissleder et al.
firstly reported a chemically orthogonal scavenger-assisted high-performance
18 F
labeling protocol using the inverse electron-demand Diels-Alder cycloaddition
reactions to synthesize
18 F labeled PARP1 inhibitor derivative (Fig. 14.6a) [46].
Using this protocol,
18 F labeled PARP1 inhibitor was prepared from the
tetrazine-tethered precursor in 59.6% RCY within 3 min, by the bioorthogonal
tetrazine-trans-cyclooctene ligation reaction with an
18 F labeled TCO synthon.
Moreover, the excess non-labeled tetrazine-tethered precursor could be removed
using a magnetic TCO scavenger resin and they could increase its molar activity. In
2012, it was reported that the bioorthogonal SPAAC based
18 F peptide labeling
reaction could provide various
18 F labeled peptide tracers under physiologicallyfriendly reaction conditions without HPLC purification process. According to this
protocol, the SPAAC reaction of ADIBO-tethered cRGD peptide was reacted with
the
18 F labeled azide synthon in aqueous media and reaction completed within
15 min to afford an
18 F-labeled cRGD peptide quantitatively [47]. Based on
chemically orthogonal scavenger-assisted purification-concept above mentioned, a
subsequent treatment of the mixture solution with the polystyrene-supported azide
scavenger resin for 20 min could allow remove the excess cold ADIBO–cRGD
precursors (Fig. 14.6b). Just after filtration and washing using a PBS, the
18 F
labeled cRGD peptide could be synthesized in a 92% RCY within the total reaction
time of 35 min. What is more appealing was that this RGD radiotracer was obtained
Fig. 14.5 Concept of the molar activity of radiolabeled molecular imaging probes for targeting.
a Low molar activity of radiotracer: bad image quality with high toxicity. b High molar activity of
radiotracer: good image quality with low toxicity
14 Bioorthogonal Reaction for Fluorine-18 Labeling
269