(BIND-014) is in phase 2 clinical trials for targeted delivery of docetaxel to
prostate-specific membrane antigen (PSMA) in metastatic prostate cancer [52].
PEG is a highly biocompatible polyether. It has been frequently used as a surface
modifier of NPs to reduce their cytotoxicity. Biodistribution studies of polymeric
NPs have shown that they are normally opsonized and removed from the bloodstream by macrophages in reticuloendothelial system (RES) such as liver and
spleen very rapidly [53]. When they are PEGylated (attachment of PEG to molecules or macrostructures), their half-time become longer and they migrate preferentially to the spleen, while smaller particles concentrate in bone marrow. The
length effect of PEG was studied using biodistribution in rats and PET imaging in
mice. Various lengths of PEG chains (1.1, 2.0, and 5.0 kDa) was grafted to poly
(methyl methacrylate-co-methacryloxysuccinimide) (PMMA-co-PMASI) [54].
After preparation of polymeric micelles, DOTA ligand was introduced to polymer
terminal as a chelator for
64 Cu. Diameters of the micelles with PEG of 1.1, 2.0, and
5.0 kDa were 9.7 ± 1.1, 17 ± 2, and 20 ± 3 nm, respectively. Biodistribution
studies and PET imaging was done after injection of
64 Cu labeled polymeric
micelles. The 5.0 kDa PEG micelle showed a slow blood clearance, and 31 ± 2%
of the dose was still in blood at 48 h after injection. It was almost ten times higher
than that of 1.1 kDa PEG micelles and twice higher than that of 2.0 kDa ones.
Liver uptake of 1.1, 2.0, and 5.0 kDa PEG micelles at 24 h from the injection was
decreased in this order and to be about 4.0, 2.8, and 1.2%ID/g, respectively.
Excretion profiles showed that the urine activity of 1.1 kDa PEG NP exhibited a
significantly higher than that of the 5.0 kDa PEG derivative. This study showed a
trend that longer PEG lengths correlates with longer blood circulation lifetimes and
lower uptake in the liver.
Polymeric NPs has been studied for vaccine adjuvants replacing aluminum salts.
Radiolabeling can reveal the fate of subcutaneously administered polymeric NPs.
125 I was labeled with poly(c-PGA-Phe), consisted of hydrophilic poly(c-glutamic
acid) and hydrophobic phenylalanine after adding tyrosine (Tyr)-residues for
radioiodination [55]. These NPs were 200 nm in diameter and had a negative
zeta-potential.
125 I has a relatively long physical half-life of 60 days and enables
monitoring a long process of excretion of NPs. Gamma scintigraphic images and
biodistribution study were followed up until 11 d post injection to the mice. The
amount of c-PGA-Phe-Tyr(
125 I) NPs at the site of injection (SOI) gradually
decreased over a week. About 3% of injection doses were remained at SOI, and
little was detected in the organs and blood all the time. At 11 d post-injection, NPs
were detected from the excretion 14 ± 4 and 59 ± 1% from feces and urine,
respectively.
Radiolabeled polymeric NPs was studied for chemoradiation therapy.
Core-crosslinked polymeric micelles (CCPM) was prepared from self-assembly and
cross-linking of poly[oligo(ethylene glycol) methyl ether methacrylate]30-b-poly(2(methacryloyloxy)ethyl 4-oxo-4-(3-(triethoxysilyl)propylamino)butanoate) [56].
177 Lu was conjugated via a chelator complex, DTPA-bz-SCN which was introduce
to CCPM.
177 Lu emits beta ray for treating tumors. In addition,
177
Lu can be used
for scintigraphy and dosimetry because it emits gamma ray. On the other hand,
118
K. W. Kang and M. G. Song
prostate-specific membrane antigen (PSMA) in metastatic prostate cancer [52].
PEG is a highly biocompatible polyether. It has been frequently used as a surface
modifier of NPs to reduce their cytotoxicity. Biodistribution studies of polymeric
NPs have shown that they are normally opsonized and removed from the bloodstream by macrophages in reticuloendothelial system (RES) such as liver and
spleen very rapidly [53]. When they are PEGylated (attachment of PEG to molecules or macrostructures), their half-time become longer and they migrate preferentially to the spleen, while smaller particles concentrate in bone marrow. The
length effect of PEG was studied using biodistribution in rats and PET imaging in
mice. Various lengths of PEG chains (1.1, 2.0, and 5.0 kDa) was grafted to poly
(methyl methacrylate-co-methacryloxysuccinimide) (PMMA-co-PMASI) [54].
After preparation of polymeric micelles, DOTA ligand was introduced to polymer
terminal as a chelator for
64 Cu. Diameters of the micelles with PEG of 1.1, 2.0, and
5.0 kDa were 9.7 ± 1.1, 17 ± 2, and 20 ± 3 nm, respectively. Biodistribution
studies and PET imaging was done after injection of
64 Cu labeled polymeric
micelles. The 5.0 kDa PEG micelle showed a slow blood clearance, and 31 ± 2%
of the dose was still in blood at 48 h after injection. It was almost ten times higher
than that of 1.1 kDa PEG micelles and twice higher than that of 2.0 kDa ones.
Liver uptake of 1.1, 2.0, and 5.0 kDa PEG micelles at 24 h from the injection was
decreased in this order and to be about 4.0, 2.8, and 1.2%ID/g, respectively.
Excretion profiles showed that the urine activity of 1.1 kDa PEG NP exhibited a
significantly higher than that of the 5.0 kDa PEG derivative. This study showed a
trend that longer PEG lengths correlates with longer blood circulation lifetimes and
lower uptake in the liver.
Polymeric NPs has been studied for vaccine adjuvants replacing aluminum salts.
Radiolabeling can reveal the fate of subcutaneously administered polymeric NPs.
125 I was labeled with poly(c-PGA-Phe), consisted of hydrophilic poly(c-glutamic
acid) and hydrophobic phenylalanine after adding tyrosine (Tyr)-residues for
radioiodination [55]. These NPs were 200 nm in diameter and had a negative
zeta-potential.
125 I has a relatively long physical half-life of 60 days and enables
monitoring a long process of excretion of NPs. Gamma scintigraphic images and
biodistribution study were followed up until 11 d post injection to the mice. The
amount of c-PGA-Phe-Tyr(
125 I) NPs at the site of injection (SOI) gradually
decreased over a week. About 3% of injection doses were remained at SOI, and
little was detected in the organs and blood all the time. At 11 d post-injection, NPs
were detected from the excretion 14 ± 4 and 59 ± 1% from feces and urine,
respectively.
Radiolabeled polymeric NPs was studied for chemoradiation therapy.
Core-crosslinked polymeric micelles (CCPM) was prepared from self-assembly and
cross-linking of poly[oligo(ethylene glycol) methyl ether methacrylate]30-b-poly(2(methacryloyloxy)ethyl 4-oxo-4-(3-(triethoxysilyl)propylamino)butanoate) [56].
177 Lu was conjugated via a chelator complex, DTPA-bz-SCN which was introduce
to CCPM.
177 Lu emits beta ray for treating tumors. In addition,
177
Lu can be used
for scintigraphy and dosimetry because it emits gamma ray. On the other hand,
118
K. W. Kang and M. G. Song