This unexpected interaction can cause the denaturation of biomolecules and the
cytotoxicity by residual copper in the bioactive products during this bioconjugation
process [6–8].
14.2 Bioorthogonal Reaction
In recent advances in molecular imaging, bioorthogonal ligation reactions played an
important role for synthesis of radiolabeled probes [9]. These bioorthogonal reaction s are useful tools to conjugate bioactive compounds with radiolabeled synthon,
highly chemoselectively without need for metal catalyst under physiologically
friendly condition i.e., in water, aqueous media or even cell media, tolerance of a
broad range of functionality [9, 10]. Among various bioorthogonal reactions, the
strain promoted alkyne azide cycloaddition (SPAAC) and the inverse Diels-Alder
tetrazine click reaction have been widely used for this purpose.
Firstly, the SPAAC reaction, which is referred to as copper-free click chemistry,
has acted as a straightforward and fast ligation method for biological applications,
as well as an alternative bioorthogonal conjugation reaction of biomolecules with
radiolabeled building blocks for the preparation of radiopharmaceuticals [9]. In this
regard, many researchers have developed a variety of cyclooctyne building blocks
for a variety of applications in molecular imaging [11–20]. Among various
cyclooctyne derivatives, aza-dibenzocyclooctyne (ADIBO) or dibenzocyclooctyne
(DIBO) compounds have been used widely with azide building blocks to rapidly
produce the corresponding triazole derivatives for efficient SPAAC reaction
(Fig. 14.1a) [21–23]. The strain promoted inverse electron-demand Diels-Alder
cycloaddition reactions of 1,2,4,5-tetrazines are known to be another popular bioconjugation method for molecular imaging applications (Fig. 14.1b). The
cycloaddition of a tetrazine with trans-cyclooctene (TCO) derivatives to the corresponding cycloocta[d]pyridazines can also provide the unusually fast reaction
rates in the absence of any catalyst under physiologically friendly condition [24].
It is well known that positron emission tomography (PET) is one of excellent
biomedical imaging modality. This PET system has been able to help early
detection, characterization, and real time monitoring of disease pathologies.
Nowadays, it is also useful for characterizing fundamental biological processes and
helping new drug developments [25, 26]. In order to obtain high-quality PET
images for this purpose, it is necessary to synthesize specific radiolabeled molecular
imaging probes using positron-emitters, such as carbon-11 (
11 C, t 1/2 = 20.4 min),
nitrogen-13 (
13 N, t 1/2 = 10 min), oxygen-15 (
15 O, t 1/2 = 2.05 min), copper-64
(
64 Cu, t 1/2 = 12.7 h), fluorine-18 (
18 F, t 1/2 = 109.8 min) [27, 28]. In particular,
18 F
is known to be the most prominent positron emitter for PET molecular imaging due
to its favorable properties as follow; (i) its minimal steric interference can allow
18 F
labeled biologically active molecules to maintain favorable interactions with the
target proteins or receptors for tracing biological processes; (ii)
18 F can be generated
easily from a cyclotron through the
18 O(p, n)
18 F nuclear reaction using [
18 O] water
264
D. W. Kim
cytotoxicity by residual copper in the bioactive products during this bioconjugation
process [6–8].
14.2 Bioorthogonal Reaction
In recent advances in molecular imaging, bioorthogonal ligation reactions played an
important role for synthesis of radiolabeled probes [9]. These bioorthogonal reaction s are useful tools to conjugate bioactive compounds with radiolabeled synthon,
highly chemoselectively without need for metal catalyst under physiologically
friendly condition i.e., in water, aqueous media or even cell media, tolerance of a
broad range of functionality [9, 10]. Among various bioorthogonal reactions, the
strain promoted alkyne azide cycloaddition (SPAAC) and the inverse Diels-Alder
tetrazine click reaction have been widely used for this purpose.
Firstly, the SPAAC reaction, which is referred to as copper-free click chemistry,
has acted as a straightforward and fast ligation method for biological applications,
as well as an alternative bioorthogonal conjugation reaction of biomolecules with
radiolabeled building blocks for the preparation of radiopharmaceuticals [9]. In this
regard, many researchers have developed a variety of cyclooctyne building blocks
for a variety of applications in molecular imaging [11–20]. Among various
cyclooctyne derivatives, aza-dibenzocyclooctyne (ADIBO) or dibenzocyclooctyne
(DIBO) compounds have been used widely with azide building blocks to rapidly
produce the corresponding triazole derivatives for efficient SPAAC reaction
(Fig. 14.1a) [21–23]. The strain promoted inverse electron-demand Diels-Alder
cycloaddition reactions of 1,2,4,5-tetrazines are known to be another popular bioconjugation method for molecular imaging applications (Fig. 14.1b). The
cycloaddition of a tetrazine with trans-cyclooctene (TCO) derivatives to the corresponding cycloocta[d]pyridazines can also provide the unusually fast reaction
rates in the absence of any catalyst under physiologically friendly condition [24].
It is well known that positron emission tomography (PET) is one of excellent
biomedical imaging modality. This PET system has been able to help early
detection, characterization, and real time monitoring of disease pathologies.
Nowadays, it is also useful for characterizing fundamental biological processes and
helping new drug developments [25, 26]. In order to obtain high-quality PET
images for this purpose, it is necessary to synthesize specific radiolabeled molecular
imaging probes using positron-emitters, such as carbon-11 (
11 C, t 1/2 = 20.4 min),
nitrogen-13 (
13 N, t 1/2 = 10 min), oxygen-15 (
15 O, t 1/2 = 2.05 min), copper-64
(
64 Cu, t 1/2 = 12.7 h), fluorine-18 (
18 F, t 1/2 = 109.8 min) [27, 28]. In particular,
18 F
is known to be the most prominent positron emitter for PET molecular imaging due
to its favorable properties as follow; (i) its minimal steric interference can allow
18 F
labeled biologically active molecules to maintain favorable interactions with the
target proteins or receptors for tracing biological processes; (ii)
18 F can be generated
easily from a cyclotron through the
18 O(p, n)
18 F nuclear reaction using [
18 O] water
264
D. W. Kim