enhanced accumulation and retention of the NPs at the diseased site via active
targeting mechanism relies on specific ligand-receptor or antibody-receptor interactions. Several studies reporting NPs modified with specific ligands such as
monoclonal antibodies [9] folic acid and peptides [10–12] as well as aptamers [13]
have been reported to date. Successful targeting depends on the selection of the
right targeting moiety, considerations for which include the expression level of
receptors, its affinity and specificity for the receptor, and ease of conjugation to the
nanoplatform. Despite the advantages gained from NP utilization, there are still
challenges that need to be addressed, such as, the uptake of NPs by the RES, in
which NPs are rapidly removed from the circulation through the liver or spleen,
thereby raising concerns about NP toxicity in these tissues. Furthermore, NP
aggregation can cause them to be trapped in the liver or lungs due to capillary
blockage [14]. Polyethylene glycol (PEG) modification of NP surface can alleviate
many of these limitations and, thus, this approach has been extensively used for a
variety of material types. An excellent review on NP PEGylation for imaging and
therapy has been published elsewhere [15].
While a great variety of materials have been proposed in the development of NS,
different imaging techniques have also been used for imaging NP-based tracers,
including magnetic resonance imaging (MRI), as well as optical and nuclear imaging
modalities techniques such as fluorescence and bioluminescence, single photon
emission computed tomography (SPECT) and positron emission tomography
(PET) [1]. In this context, nanomaterials have been extensively explored to be used
as carriers for therapeutic and/or diagnostic radioisotopes. A radiolabeled
nanoplatform must be designed to incorporate high radiostability and high specific
activity in the final product. For that, a radiolabeling method must, ideally, be quick,
safe and efficient, with minimal effect on the intrinsic properties and pharmacokinetics of the NP vector [16]. The most commonly used radiolabeling methods rely
on the use of exogenous chelators, such as 1,4,7,10-tetraazacyclododecane1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid
(NOTA), p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS) and diethylene
triamine pentaacetic acid (DTPA), which establish stable complexes with the
radioisotopes through coordination. Since the coordination chemistry is different for
every isotope, the selection of proper chelator is crucial [17]. It is important to
mention, however, that the conjugation of the chelator into the NPs could potentially
alter one or more in vivo parameter, such as biodistribution, elimination pathway,
absorption and metabolism of the final nanoconstruct [18]. Also, concerns about a
possible detachment of the isotope in vivo have compelled the need for developing
improved radiolabeling techniques. Hence, chelator-free radiolabeling has been
proposed, in which intrinsically radiolabeled NPs are synthesized using different
methods, such as specific trapping, cation exchange, proton beam activation and
synthesis using hot-plus-cold precursors [19]. Intrinsic radiolabeling of NPs has
been shown to be an attractive alternative for an easier and more realiable radiolabeling of nanomaterials [18–21].
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
15
targeting mechanism relies on specific ligand-receptor or antibody-receptor interactions. Several studies reporting NPs modified with specific ligands such as
monoclonal antibodies [9] folic acid and peptides [10–12] as well as aptamers [13]
have been reported to date. Successful targeting depends on the selection of the
right targeting moiety, considerations for which include the expression level of
receptors, its affinity and specificity for the receptor, and ease of conjugation to the
nanoplatform. Despite the advantages gained from NP utilization, there are still
challenges that need to be addressed, such as, the uptake of NPs by the RES, in
which NPs are rapidly removed from the circulation through the liver or spleen,
thereby raising concerns about NP toxicity in these tissues. Furthermore, NP
aggregation can cause them to be trapped in the liver or lungs due to capillary
blockage [14]. Polyethylene glycol (PEG) modification of NP surface can alleviate
many of these limitations and, thus, this approach has been extensively used for a
variety of material types. An excellent review on NP PEGylation for imaging and
therapy has been published elsewhere [15].
While a great variety of materials have been proposed in the development of NS,
different imaging techniques have also been used for imaging NP-based tracers,
including magnetic resonance imaging (MRI), as well as optical and nuclear imaging
modalities techniques such as fluorescence and bioluminescence, single photon
emission computed tomography (SPECT) and positron emission tomography
(PET) [1]. In this context, nanomaterials have been extensively explored to be used
as carriers for therapeutic and/or diagnostic radioisotopes. A radiolabeled
nanoplatform must be designed to incorporate high radiostability and high specific
activity in the final product. For that, a radiolabeling method must, ideally, be quick,
safe and efficient, with minimal effect on the intrinsic properties and pharmacokinetics of the NP vector [16]. The most commonly used radiolabeling methods rely
on the use of exogenous chelators, such as 1,4,7,10-tetraazacyclododecane1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid
(NOTA), p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS) and diethylene
triamine pentaacetic acid (DTPA), which establish stable complexes with the
radioisotopes through coordination. Since the coordination chemistry is different for
every isotope, the selection of proper chelator is crucial [17]. It is important to
mention, however, that the conjugation of the chelator into the NPs could potentially
alter one or more in vivo parameter, such as biodistribution, elimination pathway,
absorption and metabolism of the final nanoconstruct [18]. Also, concerns about a
possible detachment of the isotope in vivo have compelled the need for developing
improved radiolabeling techniques. Hence, chelator-free radiolabeling has been
proposed, in which intrinsically radiolabeled NPs are synthesized using different
methods, such as specific trapping, cation exchange, proton beam activation and
synthesis using hot-plus-cold precursors [19]. Intrinsic radiolabeling of NPs has
been shown to be an attractive alternative for an easier and more realiable radiolabeling of nanomaterials [18–21].
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
15