rapid accumulation in the liver (up to 30%ID/g) [79], clearly indicating a concerning aggregation in vivo.
17.2.3 Radiolabeled Gold and Copper Sulfide Nanoparticles
Ultra-small gold nanoparticles (AuNPs) have also been developed as radiological
and luminescence imaging contrast agents [27, 80–82] Gold-198 (
198 Au) intrinsically labeled, glutathione-coated 2–3 nm sized AuNPs (or GS–[
198 Au]AuNP) were
found to allow over 50% of the particles to be excreted in the urine within 24 h post
injection (Fig. 17.4a) [83]. A dynamic PET imaging of
64 Cu–NOTA–Au–GS with
a similar HD size showed a rapid renal clearance with an over 75%ID within the
first day post-injection [84] (Fig. 17.4b). Interestingly, based on dynamic PET
imaging the elimination half-life of
64 Cu–NOTA–Au–GS was estimated to be
extremely short of <6 min, which was over 130 times shorter than previously
reported similar nanoparticles based on quantification using optical imaging [83,
85]. PEGylation was found to be a useful surface modification method for ultrasmall Au nanoparticles. In one study, PEGylated AuNPs (PEG molecular weight:
1 kDa) were shown to have three times higher passive targeting efficacy when
compared with non-PEGylated GS-AuNPs [81]. Although more nuclear
imaging-based quantitative validations are warranted to confirm the above findings,
a recent study showed that renal clearance depended on the density found by
comparing heavier ultrasmall GS-coated gold with lighter silver nanoparticles [86].
Results showed that the renal clearance decreased exponentially in the early
elimination phase with an increase in particle density and that tumor targeting is
linearly dependent on the particle density. The authors further suggested that such
density dependence of the in vivo behavior might very likely originate from
density-dependent margination.
Similarly to the intrinsic labeling of
198 Au with ultrasmall Au nanoparticles,
researchers also developed renal clearable (HD <6 nm)
64 Cu-labeled CuS
nanoparticles (i.e., [
64 Cu]CuS). These nanoparticles efficiently absorbed
near-infrared light for photothermal ablation therapy, and were visible on PET
imaging [87]. About 95%ID of i.v. injected [
64 Cu]CuS was found to be excreted
intact through the kidneys within 24 h, while the RES organs showed only minimal
retention of the radioactivity. These findings were dramatically different from the
older version of [
64 Cu]CuS, which had a physical size of 11 nm, and showed
dominant liver and spleen uptake after i.v. injection [88]. Although the passive
tumor uptake of [
64 Cu]CuS in 4T1 tumors was still quite low, the authors showed
definitely a proof-of-concept study of photothermal therapy using such theranostic
nanoparticles.
Renal clearable functional nanoparticles showed greater potential for future
cancer imaging and therapy, however, great challenges still remain to find methods
to further functionalize the surface with tumor-targeting ligands and better balance
17 Size-, Shape- and Charge-Dependent Pharmacokinetics …
321
17.2.3 Radiolabeled Gold and Copper Sulfide Nanoparticles
Ultra-small gold nanoparticles (AuNPs) have also been developed as radiological
and luminescence imaging contrast agents [27, 80–82] Gold-198 (
198 Au) intrinsically labeled, glutathione-coated 2–3 nm sized AuNPs (or GS–[
198 Au]AuNP) were
found to allow over 50% of the particles to be excreted in the urine within 24 h post
injection (Fig. 17.4a) [83]. A dynamic PET imaging of
64 Cu–NOTA–Au–GS with
a similar HD size showed a rapid renal clearance with an over 75%ID within the
first day post-injection [84] (Fig. 17.4b). Interestingly, based on dynamic PET
imaging the elimination half-life of
64 Cu–NOTA–Au–GS was estimated to be
extremely short of <6 min, which was over 130 times shorter than previously
reported similar nanoparticles based on quantification using optical imaging [83,
85]. PEGylation was found to be a useful surface modification method for ultrasmall Au nanoparticles. In one study, PEGylated AuNPs (PEG molecular weight:
1 kDa) were shown to have three times higher passive targeting efficacy when
compared with non-PEGylated GS-AuNPs [81]. Although more nuclear
imaging-based quantitative validations are warranted to confirm the above findings,
a recent study showed that renal clearance depended on the density found by
comparing heavier ultrasmall GS-coated gold with lighter silver nanoparticles [86].
Results showed that the renal clearance decreased exponentially in the early
elimination phase with an increase in particle density and that tumor targeting is
linearly dependent on the particle density. The authors further suggested that such
density dependence of the in vivo behavior might very likely originate from
density-dependent margination.
Similarly to the intrinsic labeling of
198 Au with ultrasmall Au nanoparticles,
researchers also developed renal clearable (HD <6 nm)
64 Cu-labeled CuS
nanoparticles (i.e., [
64 Cu]CuS). These nanoparticles efficiently absorbed
near-infrared light for photothermal ablation therapy, and were visible on PET
imaging [87]. About 95%ID of i.v. injected [
64 Cu]CuS was found to be excreted
intact through the kidneys within 24 h, while the RES organs showed only minimal
retention of the radioactivity. These findings were dramatically different from the
older version of [
64 Cu]CuS, which had a physical size of 11 nm, and showed
dominant liver and spleen uptake after i.v. injection [88]. Although the passive
tumor uptake of [
64 Cu]CuS in 4T1 tumors was still quite low, the authors showed
definitely a proof-of-concept study of photothermal therapy using such theranostic
nanoparticles.
Renal clearable functional nanoparticles showed greater potential for future
cancer imaging and therapy, however, great challenges still remain to find methods
to further functionalize the surface with tumor-targeting ligands and better balance
17 Size-, Shape- and Charge-Dependent Pharmacokinetics …
321