Another important issue of radionanomedicine is quality control of the NPs. This
concern can also be solved by Jeong’s method, which can provide monodisperse
NPs even after the multifunctional surface modification [90]. Although Jeong’s
method has great feasibility and a future in radionanomedicine, we have to thoroughly evaluate the unexpected toxicity from lipid contents used for encapsulation
and also develop the quantification method of functional groups encapsulated on
their nanoplatforms.
11.4 Different Radiolabeling Methods
11.4.1 Extrinsic Radiolabeling
The most widely used radio-labeling method involves the use of chelators which
could coordinate with certain isotopes to form stable complexes [97]. Extrinsically
labeled NPs using chelators according to labeling methods and materials are well
summarized in the review articles by Xing et al. [98] and Enrique Morales-Avila
et al. [99]. Chelators used for this purpose include DTPA (diethylene triamine
pentaacetic acid), DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
acid), NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), and others [100, 101]
(Fig. 11.6). In 2007, Cai et al. labeled QD with
64
Cu (
64 Cu-DOTA-QD-RGD) with
conjugation of DOTA and RGD peptides.
64 Cu-DOTA-QD-RGD showed better
integrin positive tumor targeting than
64 Cu-DOTA-QD [30]. Despite the wide use
of extrinsically radiolabeled NPs, selection of the right chelator, radiolabeling
condition, alteration of pharmacokinetics and in vivo stability should always be
considered [102, 103]. Hence, in-depth knowledge of the labeling chemistry is
required for the successful extrinsic radiolabeling.
11.4.2 Intrinsic Radiolabeling
Studies regarding four different methods of intrinsically radiolabeled NPs are well
summarized in a recent review article by Goel et al. [104]. Briefly speaking these
four methods are as below. The first method is ‘Hot-plus-cold precursors’. As its
name implies, this method is performed by adding trace amount of radioactive
precursors to the non-radioactive precursors. As an example, Zhou et al. developed
intrinsically
64 Cu-labeled copper sulfide (CuS) and the NPs showed passive targeting in mouse tumor model [7]. The second method is ‘Specific trapping’, which
is a specific absorption of certain isotopes into appropriate NPs. Intrinsically
radioactive upconverting NPs were made by trapping
18 F to rare-earth NPs, [
18 F]
NaYF4:Gd,Yb,Er [22]. The third strategy is ‘Cation exchange’, which have been
utilized largely in ionic and semiconductor nanocrystals. This method is not yet
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D. S. Lee et al.
concern can also be solved by Jeong’s method, which can provide monodisperse
NPs even after the multifunctional surface modification [90]. Although Jeong’s
method has great feasibility and a future in radionanomedicine, we have to thoroughly evaluate the unexpected toxicity from lipid contents used for encapsulation
and also develop the quantification method of functional groups encapsulated on
their nanoplatforms.
11.4 Different Radiolabeling Methods
11.4.1 Extrinsic Radiolabeling
The most widely used radio-labeling method involves the use of chelators which
could coordinate with certain isotopes to form stable complexes [97]. Extrinsically
labeled NPs using chelators according to labeling methods and materials are well
summarized in the review articles by Xing et al. [98] and Enrique Morales-Avila
et al. [99]. Chelators used for this purpose include DTPA (diethylene triamine
pentaacetic acid), DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
acid), NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), and others [100, 101]
(Fig. 11.6). In 2007, Cai et al. labeled QD with
64
Cu (
64 Cu-DOTA-QD-RGD) with
conjugation of DOTA and RGD peptides.
64 Cu-DOTA-QD-RGD showed better
integrin positive tumor targeting than
64 Cu-DOTA-QD [30]. Despite the wide use
of extrinsically radiolabeled NPs, selection of the right chelator, radiolabeling
condition, alteration of pharmacokinetics and in vivo stability should always be
considered [102, 103]. Hence, in-depth knowledge of the labeling chemistry is
required for the successful extrinsic radiolabeling.
11.4.2 Intrinsic Radiolabeling
Studies regarding four different methods of intrinsically radiolabeled NPs are well
summarized in a recent review article by Goel et al. [104]. Briefly speaking these
four methods are as below. The first method is ‘Hot-plus-cold precursors’. As its
name implies, this method is performed by adding trace amount of radioactive
precursors to the non-radioactive precursors. As an example, Zhou et al. developed
intrinsically
64 Cu-labeled copper sulfide (CuS) and the NPs showed passive targeting in mouse tumor model [7]. The second method is ‘Specific trapping’, which
is a specific absorption of certain isotopes into appropriate NPs. Intrinsically
radioactive upconverting NPs were made by trapping
18 F to rare-earth NPs, [
18 F]
NaYF4:Gd,Yb,Er [22]. The third strategy is ‘Cation exchange’, which have been
utilized largely in ionic and semiconductor nanocrystals. This method is not yet
220
D. S. Lee et al.