23.7 Therapy with Alpha Emitter-Labeled Nanoparticles
Alpha emitters have also been investigated as therapeutic radionuclides for the
conjugation with nanoparticles. Alpha emitters have desirable characteristics for
cancer therapy, and they are best suited for the therapy of invasive tumor cells. NPs
labeled with
213 Bi were intratumorally injected in 5 patients for the treatment of
glioma [33]. In this clinical trial, sufficient intratumoral distribution was achieved in
patients with rather small tumors, whereas the intratumoral distribution of
radioactivity was less homogenous in larger tumors. Other alpha emitters with
relatively longer half-life such as
225 Ac have been investigated for the treatment of
large tumors. In addition to the longe half-life,
225 Ac is advantageous that it emits 4
alpha-particles in the decay chain:
221 Fr,
217
At and
213 Bi. Therefore,
225 Ac could be
a good candidate to improve the efficacy in treating large tumors, since it has a
longe half-life and a cascading nature of decay. However, an appropriate strategy,
i.e. encapsulation is required to keep the radionuclides within NPs, because
225
Ac
has such a long half-life of 10 days.
The cascading decay of alpha emitters could be a limitation in the clinical
application of radionanomedicine therapeutics. The potential release of daughter
radionuclides should be considered in the biodistribution of NPs radiolabeled with
alpha emitters. The possibility of chemical complex formation with daughter
radionuclides should also be taken into consideration. In particular, daughter
radionuclides are of concern to their off-target effect, especially when the chelation
cannot retain daughter radionuclides sufficiently. The recoil can also occur when the
heavy alpha particles break the chemical bonds, to leave the nucleus, to change the
chemical properties of the daughter radionuclide [34]. In reality, daughter radionuclides could be retained poorly, though a variety of chelators have been investigated
for
225
Ac complex [35, 36]. In addition to these disadvantages, the insufficient supply
of
225
Ac could limit their vigorous use in the clinical application of
225
Ac labeled
NPs. To overcome these limitations, McLaughlin et al. designed a core-shell NP
using GdPO 4 to sequester the daughters within the NPs [37]. In this study, the GdPO 4
shell was able to retain the majority of the decay-chain daughter radionuclides (88%
of the
221
Fr) while reducing the energy of the alpha-particles emitted by only 0.2%.
References
1. D.S. Lee, H.J. Im, Y.S. Lee, Radionanomedicine: widened perspectives of molecular
theragnosis. Nanomedicine 11(4), 795–810 (2015)
2. V.E. Kagan, H. Bayir, A.A. Shvedova, Nanomedicine and nanotoxicology: two sides of the
same coin. Nanomedicine 1(4), 313–316 (2005)
3. M.C. Garnett, P. Kallinteri, Nanomedicines and nanotoxicology: some physiological
principles. Occup. Med. (Lond.) 56(5), 307–311 (2006)
4. M.A. Maurer-Jones, K.C. Bantz, S.A. Love, B.J. Marquis, C.L. Haynes, Toxicity of
therapeutic nanoparticles. Nanomedicine (Lond.) 4(2), 219–241 (2009)
440
S. W. Oh and D. S. Lee
Alpha emitters have also been investigated as therapeutic radionuclides for the
conjugation with nanoparticles. Alpha emitters have desirable characteristics for
cancer therapy, and they are best suited for the therapy of invasive tumor cells. NPs
labeled with
213 Bi were intratumorally injected in 5 patients for the treatment of
glioma [33]. In this clinical trial, sufficient intratumoral distribution was achieved in
patients with rather small tumors, whereas the intratumoral distribution of
radioactivity was less homogenous in larger tumors. Other alpha emitters with
relatively longer half-life such as
225 Ac have been investigated for the treatment of
large tumors. In addition to the longe half-life,
225 Ac is advantageous that it emits 4
alpha-particles in the decay chain:
221 Fr,
217
At and
213 Bi. Therefore,
225 Ac could be
a good candidate to improve the efficacy in treating large tumors, since it has a
longe half-life and a cascading nature of decay. However, an appropriate strategy,
i.e. encapsulation is required to keep the radionuclides within NPs, because
225
Ac
has such a long half-life of 10 days.
The cascading decay of alpha emitters could be a limitation in the clinical
application of radionanomedicine therapeutics. The potential release of daughter
radionuclides should be considered in the biodistribution of NPs radiolabeled with
alpha emitters. The possibility of chemical complex formation with daughter
radionuclides should also be taken into consideration. In particular, daughter
radionuclides are of concern to their off-target effect, especially when the chelation
cannot retain daughter radionuclides sufficiently. The recoil can also occur when the
heavy alpha particles break the chemical bonds, to leave the nucleus, to change the
chemical properties of the daughter radionuclide [34]. In reality, daughter radionuclides could be retained poorly, though a variety of chelators have been investigated
for
225
Ac complex [35, 36]. In addition to these disadvantages, the insufficient supply
of
225
Ac could limit their vigorous use in the clinical application of
225
Ac labeled
NPs. To overcome these limitations, McLaughlin et al. designed a core-shell NP
using GdPO 4 to sequester the daughters within the NPs [37]. In this study, the GdPO 4
shell was able to retain the majority of the decay-chain daughter radionuclides (88%
of the
221
Fr) while reducing the energy of the alpha-particles emitted by only 0.2%.
References
1. D.S. Lee, H.J. Im, Y.S. Lee, Radionanomedicine: widened perspectives of molecular
theragnosis. Nanomedicine 11(4), 795–810 (2015)
2. V.E. Kagan, H. Bayir, A.A. Shvedova, Nanomedicine and nanotoxicology: two sides of the
same coin. Nanomedicine 1(4), 313–316 (2005)
3. M.C. Garnett, P. Kallinteri, Nanomedicines and nanotoxicology: some physiological
principles. Occup. Med. (Lond.) 56(5), 307–311 (2006)
4. M.A. Maurer-Jones, K.C. Bantz, S.A. Love, B.J. Marquis, C.L. Haynes, Toxicity of
therapeutic nanoparticles. Nanomedicine (Lond.) 4(2), 219–241 (2009)
440
S. W. Oh and D. S. Lee