load sorafenib which were delivered to the tumor site. Furthermore, long term
retention of MNPs in the tumor tissues was also observed by comparing the tumor
uptake value at 4 h post injection with that at 24 h post injection, ensuring the
gradual release of sorafenib from its carrier at the tumor site.
Sun et al. has recently made use of
64 Cu and
89 Zr labeled POVF micelles to
monitor their in vivo bio-distribution as well as predict corresponding therapeutic
outcomes (unpublished data). Specifically, via SPAAC based click chemistry
approach, paclitaxel (PTX) loaded POVF micelles, which contained free azide
groups on their surface, were labeled with either
64 Cu or
89 Zr for monitoring their
tumor uptakes at early time points (1, 4, and 8 h) and late time points (24, 48, 72,
96 h), respectively. Results indicated that the accumulation of the designed drug
delivery system in tumor tissues started as early as 4 h and maintained at a high
level (around 10%ID/g) for up to 72 h. Based on the in vitro PTX release curve,
most of PTX would still be kept in the designed micelles at 4 h time points,
indicating that an efficient drug delivery to tumor could be anticipated with this
system. Subsequent in vivo therapeutic study showed significant reduction of tumor
size in mice treated with this PTX loaded POVF compared with the vehicle control
group, demonstrating its potential clinical value for the cancer treatment.
12.5.3 Applied in Internal Radiotherapy
Targeted internal radiotherapy has been considered as a promising radiotherapy
strategy due to significantly reduced radio exposure to normal organs as compared
with traditional radiotherapy using external radio beams. Nanoparticles, which can
not only target the tumor tissues via EPR effects but also provide prominent loading
capacity for delivery of therapeutic radionuclides, could serve as an ideal device for
targeted internal radiotherapy. Pioneering clinical imaging studies revealed an
effective targeting of solid tumors in patients via nanoparticles, indicating the
potential of using radiolabeled nanoparticles to deliver therapeutic radioisotopes for
internal radiotherapy [61].
Initial trial of internal radiotherapy using nanoparticles employed
188 Re as the b
source. Excellent suppression of tumor growth was observed while side effects were
minimized in the head and neck squamous cell carcinoma xenograft model [65].
Co-labeling of
111 In and
188 Re for nanotargeted radio-therapeutics was also
reported in which
111 In provided the Auger electron for killing single tumor cells or
small tumor cluster while
188 Re provided the high-energy beta ray for killing large
tumor clusters [62, 66, 67].
However,
188 Re has a half-life time of 17 h, which is a little bit shorter compared
with the time frame of the EPR process. Therefore, other beta emitter with more
compatible half-life time have also been investigated. One ideal alternative choice is
90 Y with a half-life time of 64 h. In particular, lipid nanoparticles conjugated with
anti VEGFR-2 antibody has been labeled with
90 Y and evaluated in vivo for their
internal radio therapeutic efficacy [68]. Growth of tumor was obviously inhibited as
244
Y.-S. Lee et al.
retention of MNPs in the tumor tissues was also observed by comparing the tumor
uptake value at 4 h post injection with that at 24 h post injection, ensuring the
gradual release of sorafenib from its carrier at the tumor site.
Sun et al. has recently made use of
64 Cu and
89 Zr labeled POVF micelles to
monitor their in vivo bio-distribution as well as predict corresponding therapeutic
outcomes (unpublished data). Specifically, via SPAAC based click chemistry
approach, paclitaxel (PTX) loaded POVF micelles, which contained free azide
groups on their surface, were labeled with either
64 Cu or
89 Zr for monitoring their
tumor uptakes at early time points (1, 4, and 8 h) and late time points (24, 48, 72,
96 h), respectively. Results indicated that the accumulation of the designed drug
delivery system in tumor tissues started as early as 4 h and maintained at a high
level (around 10%ID/g) for up to 72 h. Based on the in vitro PTX release curve,
most of PTX would still be kept in the designed micelles at 4 h time points,
indicating that an efficient drug delivery to tumor could be anticipated with this
system. Subsequent in vivo therapeutic study showed significant reduction of tumor
size in mice treated with this PTX loaded POVF compared with the vehicle control
group, demonstrating its potential clinical value for the cancer treatment.
12.5.3 Applied in Internal Radiotherapy
Targeted internal radiotherapy has been considered as a promising radiotherapy
strategy due to significantly reduced radio exposure to normal organs as compared
with traditional radiotherapy using external radio beams. Nanoparticles, which can
not only target the tumor tissues via EPR effects but also provide prominent loading
capacity for delivery of therapeutic radionuclides, could serve as an ideal device for
targeted internal radiotherapy. Pioneering clinical imaging studies revealed an
effective targeting of solid tumors in patients via nanoparticles, indicating the
potential of using radiolabeled nanoparticles to deliver therapeutic radioisotopes for
internal radiotherapy [61].
Initial trial of internal radiotherapy using nanoparticles employed
188 Re as the b
source. Excellent suppression of tumor growth was observed while side effects were
minimized in the head and neck squamous cell carcinoma xenograft model [65].
Co-labeling of
111 In and
188 Re for nanotargeted radio-therapeutics was also
reported in which
111 In provided the Auger electron for killing single tumor cells or
small tumor cluster while
188 Re provided the high-energy beta ray for killing large
tumor clusters [62, 66, 67].
However,
188 Re has a half-life time of 17 h, which is a little bit shorter compared
with the time frame of the EPR process. Therefore, other beta emitter with more
compatible half-life time have also been investigated. One ideal alternative choice is
90 Y with a half-life time of 64 h. In particular, lipid nanoparticles conjugated with
anti VEGFR-2 antibody has been labeled with
90 Y and evaluated in vivo for their
internal radio therapeutic efficacy [68]. Growth of tumor was obviously inhibited as
244
Y.-S. Lee et al.