23.5 Administration Methods of Radiolabeled
Nanoparticles for Therapy
Therapeutic nanoparticles are usually delivered to solid tumor in a non-specific
way, when they are administered systemically. NP accumulation in the solid tumor
is mainly dependent on the non-specific mechanism as known as the enhanced
permeability and retention (EPR) effect. The EPR effect is mainly contributed to
leaky tumor vasculature and poor lymphatic drainage [21, 22]. However, the EPR
effect is often inefficient to achieve a sufficient therapeutic effect, compared with
specific drug delivery. Thus, various strategies have been developed, so as to
adequately treat solid tumors by delivering sufficient amount of NPs to the tumor.
For example, thermal stimuli can be given before systemic administration of the
NPs to enhance the EPR effect. Local application of RF damage prior to NPs
injection greatly increased the accumulation of NPs in the thermal ablation site [23].
This enhancement of the EPR effect seemed as the leakage of NPs expanded into
the tumor and the NPs retained within a wide range of the region associated with
the thermally induced inflammation.
In addition to this efficiency problem of the targeted delivery, there are several
limitations in the systemic administration of the NPs. Nanosized materials are
mainly eliminated by the mononuclear phagocytic system (or reticuloendothelial
systems), and thus liver and spleen uptake could be a major obstacle to the use of
systemically administered NPs for cancer treatment [24]. To overcome this problem, various strategies were proposed to improve pharmacokinetic profiles and
enhance the therapeutic efficacy, e.g. changing the administration route. Direct
image-guided intratumoral administration of therapeutic agents is currently
undergoing evaluation. Intratumorally administered radiotherapeutic NPs seem to
be a viable option for the use in cancer patients.
Locally administered radionuclide therapy can be considered as brachytherapy
that is a localized and precise form of therapy delivering radiation in a short
distance. Brachytherapy using radiolabeled NPs is different from the current typical
brachytherapy in several aspects. Radiolabeled NPs are well dispersed and retained
in solid tumors, giving a high radiation dose to the tumor while reducing the
radiation exposure to the surrounding healthy tissues. A metallofullerene-based
nanoplatform carrying
177 Lu was developed as brachytherapy for brain tumor [24].
This radiolabeled NPs successfully reduced tumor growth rate in a mice tumor
model, and it remained in the brain tumor region.
177 Lu-DOTA administered alone
was not effective in comparison to radiolabeled NPs conjugated with nanoplatforms, because it rapidly cleared from the brain tumor [25, 26]. Phillips et al.
reported that gliomas of a rat model were treated with absorbed doses as high as
1700 Gray (Gy) by intratumoral administration of
186 Re-liposome NPs without
significant toxicity to adjacent normal brain tissues [27]. In addition, their
nanometer size permitted diffusion from the injection site to all over the tumor,
giving further homogeneous radiation dose to the entire tumor. Long range of
438
S. W. Oh and D. S. Lee
Nanoparticles for Therapy
Therapeutic nanoparticles are usually delivered to solid tumor in a non-specific
way, when they are administered systemically. NP accumulation in the solid tumor
is mainly dependent on the non-specific mechanism as known as the enhanced
permeability and retention (EPR) effect. The EPR effect is mainly contributed to
leaky tumor vasculature and poor lymphatic drainage [21, 22]. However, the EPR
effect is often inefficient to achieve a sufficient therapeutic effect, compared with
specific drug delivery. Thus, various strategies have been developed, so as to
adequately treat solid tumors by delivering sufficient amount of NPs to the tumor.
For example, thermal stimuli can be given before systemic administration of the
NPs to enhance the EPR effect. Local application of RF damage prior to NPs
injection greatly increased the accumulation of NPs in the thermal ablation site [23].
This enhancement of the EPR effect seemed as the leakage of NPs expanded into
the tumor and the NPs retained within a wide range of the region associated with
the thermally induced inflammation.
In addition to this efficiency problem of the targeted delivery, there are several
limitations in the systemic administration of the NPs. Nanosized materials are
mainly eliminated by the mononuclear phagocytic system (or reticuloendothelial
systems), and thus liver and spleen uptake could be a major obstacle to the use of
systemically administered NPs for cancer treatment [24]. To overcome this problem, various strategies were proposed to improve pharmacokinetic profiles and
enhance the therapeutic efficacy, e.g. changing the administration route. Direct
image-guided intratumoral administration of therapeutic agents is currently
undergoing evaluation. Intratumorally administered radiotherapeutic NPs seem to
be a viable option for the use in cancer patients.
Locally administered radionuclide therapy can be considered as brachytherapy
that is a localized and precise form of therapy delivering radiation in a short
distance. Brachytherapy using radiolabeled NPs is different from the current typical
brachytherapy in several aspects. Radiolabeled NPs are well dispersed and retained
in solid tumors, giving a high radiation dose to the tumor while reducing the
radiation exposure to the surrounding healthy tissues. A metallofullerene-based
nanoplatform carrying
177 Lu was developed as brachytherapy for brain tumor [24].
This radiolabeled NPs successfully reduced tumor growth rate in a mice tumor
model, and it remained in the brain tumor region.
177 Lu-DOTA administered alone
was not effective in comparison to radiolabeled NPs conjugated with nanoplatforms, because it rapidly cleared from the brain tumor [25, 26]. Phillips et al.
reported that gliomas of a rat model were treated with absorbed doses as high as
1700 Gray (Gy) by intratumoral administration of
186 Re-liposome NPs without
significant toxicity to adjacent normal brain tissues [27]. In addition, their
nanometer size permitted diffusion from the injection site to all over the tumor,
giving further homogeneous radiation dose to the entire tumor. Long range of
438
S. W. Oh and D. S. Lee