the purification and modification. Another beauty of click chemistry for nanomedicine is the avoidance of harsh reaction condition, such as high/low pH, temperature, or reducing/oxidizing conditions, which result in the aggregation of
nanomaterials or degradation of biomolecules. Numerous nanomedicine platforms
have been proposed and used in in vitro assay, in vivo imaging, drug delivery, or
theranostics. However, in considering manufacturing or commercialization of radionanomedicine platform, still there are much rooms to be improved. In this
chapter, we focus on the current status for the ‘clickable’ nanomedicine platforms
and how we can or will be able to reach the goal of clinical translation using this
technology.
The key concept of “click chemistry”, which was firstly coined by K. Barry
Sharpless group in 2001, is the any kind of chemical reaction that can be easily and
rapidly achieved [1]. Following this concept, great progress have been achieved in
the field of radiochemistry and nanomedicine [2–4]. Click chemistry can be used
for the surface modification of nanomedicine, such as hydrophilization, target
molecule ligation, therapeutic drug conjugation, labeling sensor molecules, such as
fluorescence dye or radioisotope. By the conventional step-by-step chemical
modification method of nanomaterials, two or more combination of those modifications can by hardly achieved, because of the low yield of the purification after
each modification step. Another beauty of click chemistry for nanomedicine is the
avoidance of harsh reaction condition, such as high/low pH, temperature, or
reductant/oxidant, which can result in the aggregation of nanomaterials or degradation of biomolecules.
Numerous nanomedicine platforms have been proposed and used in in vitro
assay, in vivo imaging, drug delivery, or theragnosis. However, in considering
manufacturing or commercialization of nanomedicine platform, still there are so
many things to be improved. In this chapter, we focus on the current status for the
“clickable” radionanomedicine platform and how we can or will be able to reach the
goal of clinical translation.
12.1 Click Chemistry Overview
Cu(I)-catalyzed azide-alkyne cycloaddtion (CuAAC) [5], strain-promoted
azide-alkyne cycloaddition (SPAAC) [6], and inverse electron demand DielsAlder cycloaddition (iEDDA) using tetrazine and trans-cyclooctene (TCO) [7] are
most widely used click reaction in radiochemistry and nanomedicine application
(Fig. 12.1). Relatively aged-reaction in organic chemistry, CuAAC reaction has
been more frequently used in radiolabeling. However, Cu(I/II) cations accidentally
formed Cu-peptide complexes in
18 F labeling using CuAAC [8]. This problem is
more complicated in radiolabeling with radiometals and chelating agent, because
the labeled radiometal-chelate complex could be trans-chelated by cold Cu in click
232
Y.-S. Lee et al.
nanomaterials or degradation of biomolecules. Numerous nanomedicine platforms
have been proposed and used in in vitro assay, in vivo imaging, drug delivery, or
theranostics. However, in considering manufacturing or commercialization of radionanomedicine platform, still there are much rooms to be improved. In this
chapter, we focus on the current status for the ‘clickable’ nanomedicine platforms
and how we can or will be able to reach the goal of clinical translation using this
technology.
The key concept of “click chemistry”, which was firstly coined by K. Barry
Sharpless group in 2001, is the any kind of chemical reaction that can be easily and
rapidly achieved [1]. Following this concept, great progress have been achieved in
the field of radiochemistry and nanomedicine [2–4]. Click chemistry can be used
for the surface modification of nanomedicine, such as hydrophilization, target
molecule ligation, therapeutic drug conjugation, labeling sensor molecules, such as
fluorescence dye or radioisotope. By the conventional step-by-step chemical
modification method of nanomaterials, two or more combination of those modifications can by hardly achieved, because of the low yield of the purification after
each modification step. Another beauty of click chemistry for nanomedicine is the
avoidance of harsh reaction condition, such as high/low pH, temperature, or
reductant/oxidant, which can result in the aggregation of nanomaterials or degradation of biomolecules.
Numerous nanomedicine platforms have been proposed and used in in vitro
assay, in vivo imaging, drug delivery, or theragnosis. However, in considering
manufacturing or commercialization of nanomedicine platform, still there are so
many things to be improved. In this chapter, we focus on the current status for the
“clickable” radionanomedicine platform and how we can or will be able to reach the
goal of clinical translation.
12.1 Click Chemistry Overview
Cu(I)-catalyzed azide-alkyne cycloaddtion (CuAAC) [5], strain-promoted
azide-alkyne cycloaddition (SPAAC) [6], and inverse electron demand DielsAlder cycloaddition (iEDDA) using tetrazine and trans-cyclooctene (TCO) [7] are
most widely used click reaction in radiochemistry and nanomedicine application
(Fig. 12.1). Relatively aged-reaction in organic chemistry, CuAAC reaction has
been more frequently used in radiolabeling. However, Cu(I/II) cations accidentally
formed Cu-peptide complexes in
18 F labeling using CuAAC [8]. This problem is
more complicated in radiolabeling with radiometals and chelating agent, because
the labeled radiometal-chelate complex could be trans-chelated by cold Cu in click
232
Y.-S. Lee et al.