12.4 Radiolabeling
Radionanomedicine can be used for diagnosis or therapy or theranosis of certain
disease. For in vivo or clinical application, the radiolabeling of nanomaterials
should be done by easy- and fast-way and this step should be located in just before
in vivo administration. Radiolabeled nanomaterials should be stable for certain time
in vitro and in vivo after the radiolabeling because the in vitro and in vivo
metabolite can affect the imaging or therapeutic efficacy of radiolabeled
nanomaterials.
There are two types of radiolabeling method, extrinsic and intrinsic method.
Extrinsic method is the most widely used method for radiolabeling of nanomaterials, and the chelator modified nanomaterials can be labeled with radioisotopes.
The click radiolabeling is also categorized as extrinsic method. Intrinsic method is
the radiolabeling of the nanoparticle core or nanoparticle surface. Extrinsic method
can be divided into two ways, pre- and post-labeling. Like click chemistry,
pre-labeling can be used for the nanomaterials containing the conjugation motifs,
such as click chemicals, on the surface and post-labeling method for the chelators
on the surface.
Click chemistry has advantages over conventional chelate labeling method. First,
using click chemistry, the nanomaterials may not meet the radiolabeling condition
directly, such as low or high pH, high temperature, in the pre-labeling method,
therefore this method will be the better choice for the acid/base or high
temperature-labile nanomaterials. Zeng et al. has reported an approach to label
shell-cross-linked nanoparticles with
64 Cu via metal free click chemistry [56].
Specifically,
64 Cu was complexed with DOTA functionalized with a DBCO group,
which was subsequently conjugated with nanoparticles bearing azide group to
generate the desired
64 Cu labeled nanoparticles. Second, labeling via the click
chemistry offers the flexibility to select radioisotopes according to the requirement
of the study by conjugating nanoparticles bearing click chemistry motifs with
different chelators functionalized with corresponding complimentary click chemistry motifs, unlike the traditional approach in which a specific chelator has been
attached to nanoparticles thus restricting the selection of radio isotopes (e.g. DFO
conjugated nanoparticles can only be labeled by
89 Zr). Third, click chemistry
provides the possibility to conduct the labeling of nanoparticles in vivo via pretargeting strategies. In particular, nanoparticles functionalized with a click reaction
moeity could be administrated in advance to allow sufficient accumulation at the
tumor site and enough clearance from blood, and then the radioisotope-chelator
complex bearing the corresponding other click reaction moiety could be injected,
which could significantly reduce the uptake in normal organs and consequently
improving tumor/non-tumor ratios substantially [57].
As we discussed above, in vivo integrity of radiolabeled nanomaterials is very
important because that can affect the imaging or therapeutic efficacy. Recently,
there are exactly opposite results that the extrinsically labeled radioisotope can or
cannot be detached from nanomaterials published in same year. Kreyling et al.
12 Click Chemistry for Radionanomedicine Platform
241
Radionanomedicine can be used for diagnosis or therapy or theranosis of certain
disease. For in vivo or clinical application, the radiolabeling of nanomaterials
should be done by easy- and fast-way and this step should be located in just before
in vivo administration. Radiolabeled nanomaterials should be stable for certain time
in vitro and in vivo after the radiolabeling because the in vitro and in vivo
metabolite can affect the imaging or therapeutic efficacy of radiolabeled
nanomaterials.
There are two types of radiolabeling method, extrinsic and intrinsic method.
Extrinsic method is the most widely used method for radiolabeling of nanomaterials, and the chelator modified nanomaterials can be labeled with radioisotopes.
The click radiolabeling is also categorized as extrinsic method. Intrinsic method is
the radiolabeling of the nanoparticle core or nanoparticle surface. Extrinsic method
can be divided into two ways, pre- and post-labeling. Like click chemistry,
pre-labeling can be used for the nanomaterials containing the conjugation motifs,
such as click chemicals, on the surface and post-labeling method for the chelators
on the surface.
Click chemistry has advantages over conventional chelate labeling method. First,
using click chemistry, the nanomaterials may not meet the radiolabeling condition
directly, such as low or high pH, high temperature, in the pre-labeling method,
therefore this method will be the better choice for the acid/base or high
temperature-labile nanomaterials. Zeng et al. has reported an approach to label
shell-cross-linked nanoparticles with
64 Cu via metal free click chemistry [56].
Specifically,
64 Cu was complexed with DOTA functionalized with a DBCO group,
which was subsequently conjugated with nanoparticles bearing azide group to
generate the desired
64 Cu labeled nanoparticles. Second, labeling via the click
chemistry offers the flexibility to select radioisotopes according to the requirement
of the study by conjugating nanoparticles bearing click chemistry motifs with
different chelators functionalized with corresponding complimentary click chemistry motifs, unlike the traditional approach in which a specific chelator has been
attached to nanoparticles thus restricting the selection of radio isotopes (e.g. DFO
conjugated nanoparticles can only be labeled by
89 Zr). Third, click chemistry
provides the possibility to conduct the labeling of nanoparticles in vivo via pretargeting strategies. In particular, nanoparticles functionalized with a click reaction
moeity could be administrated in advance to allow sufficient accumulation at the
tumor site and enough clearance from blood, and then the radioisotope-chelator
complex bearing the corresponding other click reaction moiety could be injected,
which could significantly reduce the uptake in normal organs and consequently
improving tumor/non-tumor ratios substantially [57].
As we discussed above, in vivo integrity of radiolabeled nanomaterials is very
important because that can affect the imaging or therapeutic efficacy. Recently,
there are exactly opposite results that the extrinsically labeled radioisotope can or
cannot be detached from nanomaterials published in same year. Kreyling et al.
12 Click Chemistry for Radionanomedicine Platform
241