Nanoradiopharmaceuticals Based on Alpha Emitters: Recent Developments for Medical Applications
Abstract
:1. Introduction
2. Alpha Emitters Used in TAT
2.1. Actinium-225 (225Ac)
2.2. Astatine-211 (211At)
2.3. Bismuth-213 (213Bi)
2.4. Lead-212 (212Pb)
2.5. Radium-223 (223Ra)
2.6. Thorium-226 (226Th)
2.7. Terbium-149 (149Tb)
3. Alpha Emitters in Medical Applications
4. Recoil Energy
5. Strategies
5.1. Encapsulation of Radionuclides in a Nanocarrier
5.2. Targeting Vehicle
5.3. Local Administration
6. Chelating Agents
6.1. 225Ac
6.2. 212Pb
6.3. 212/213Bi
6.4. 223Ra
6.5. 149Tb
6.6. 226/227Th
6.7. 211At
7. Targeting Vectors
8. Nanoradiopharmaceuticals Based on Alpha Emitters
Radionuclide | Nanoparticle (Type) | Retention/Release of Daughter Nuclides | Labeling Yield | Size | Ref |
---|---|---|---|---|---|
225Ac | 225Ac(La(225Ac)PO4) |
| 66% | 3–5 nm | [74] |
Multilayered {La0.5Gd0.5}PO4@GdPO4@Au doped with 225Ac |
| ~76% | 27 nm | [31] | |
Multilayer {La0.5Gd0.5}(225Ac)PO4@4GdPO4 shell@Au |
| --- | --- | [77] | |
Multilayer {Gd0.75La0.25}(225Ac)PO4@4 LaPO4 shell@Au |
| 76% | 19.9 ± 6.5 nm | [78] | |
Gadolinium vanadate (GdVO4) |
| --- | --- | [24] | |
Gadolinium vanadate core (Gd(225Ac)VO4) and core + 2 shell (Gd(225Ac)VO4/2GdVO4) |
| Yield of 225Ac was 77.1 ± 13.2% and 96.6 ± 1.6% for core and core + 2 shell, respectively Yield of 227Th was 62.9 ± 2.7% and 81.9 ± 1.2% for core and core + 2 shell, respectively | 3.6 ± 0.9 nm for core and 4.4 ± 1.0 nm for core + 2 shell | [79] | |
Gd0.8Eu0.2VO4 core and core + 2 shells |
| Yield core was 41.1 ± 16.5%, shells increased the yield up to 55% | 6.1 ± 1.4 nm for core and 12.4 ± 2.0 nm for core + 2 shells | [80] | |
Liposomes: Pegylated liposomes membrane charge (zwitterionic and cationic) |
| 6.4–10.0% | 200/400/650 nm | [11] | |
Liposomes |
| 55–73% | 121 ± 6 nm | [81] | |
Liposomes |
| 58.0–85.6% | 107 ± 2 nm | [82] | |
Multivesicular liposomes (MUVELs) |
| --- | --- | [83] | |
Polymersomes |
| 213Bi was 83 ± 75% (100 nm) 225Ac was 67 ± 0.8% (100 nm) | 100, 200, 400, and 800 nm | [28] | |
Double-layered polymersomes |
| --- | 300–800 nm | [26] | |
Polymersomes |
| 89 ± 0.6% | 100/200/400/800 nm | [84] | |
Polymerosomes | --- | >90% for 111In and >64% for 225Ac | --- | [85] | |
Polymerosomes |
| 54–59% | 97 ± 37 nm | [86] | |
Fullerenes: 225Ac metallofullerene | --- | --- | --- | [87] | |
TiO2 |
| 99.8 ± 2.1% | 25 nm | [88] | |
Carbon nanotubes |
| --- | --- | [89] | |
Carbon nanotubes | --- | ~95% | --- | [90] | |
Lipid vehicle |
| 62.7 ± 14.6% | 106 ± 4 nm | [91] | |
223Ra | LnPO4 core and core + 2 shells NPs (Ln = La, Gd) |
| 91% for LaPO4 core + 2 shell | 3.4 nm for core and 6.3 nm for core + 2 shells | [75] |
Hydroxyapatite (HA) |
| >95% | 15 nm | [92] | |
Hydroxyapatite (nHAp) and titanium dioxide (nTiO2) |
| ~95% | --- | [93] | |
Hydroxyapatite (HAP) | --- | 98% | Width up to 100 nm and length up to 500 nm | [94] | |
Hydroxyapatite (HAP) | --- | 98% | 900–1000 μm | [95] | |
Liposomes |
| 223Ra was 78 ± 6% 228Ac was 61 ± 8% | --- | [96] | |
Liposomes: Pegylated liposomal doxorubicin (PLD) |
| 51–67% | 80 nm | [97] | |
223/224/225Ra-nanozeolite (NaA) |
| 99.9% | 30–70 nm | [22] | |
223Ra-labeled nanozeolite |
| 99.9% | 50–80 nm | [76] | |
BaSO4 | --- | 20% | 140 nm | [98] | |
Superparamagnetic iron oxide nanoparticles Fe3O4 SPIONS |
| 85–99% (PBS) | 4–26 nm | [99] | |
Reduced graphite oxide |
| Sorption was 10% for 223Ra, 90% of 99mTc, 80–100% for 207Bi and 90Y | 4–6 nm | [100] | |
Polyoxopalladates (Pd-POM): [224Ra]Na-a(Ra)Pd15 |
| --- | --- | [101] | |
Calcium carbonate microparticles |
| >80% of 224Ra and 212Pb (daughter nuclide) | --- | [102] | |
211At | Silver core coated by PEO shell | --- | 50–97% | 18.3–34.7 nm | [73] |
Ultrashort nanotubes |
| 77.7–91.3% | 20–50 nm in length and 1 nm diameter | [103] | |
Gold nanoparticles (AuNPs) | --- | >99% | 5 and 15 nm | [104] | |
Gold nanoparticles (AuNPs) | --- | >99% | 5 nm | [105] | |
212Pb | Liposomes | --- | 75% | --- | [106] |
Liposomes |
| 90 ± 2% | --- | [107] | |
Hydroxyapatite (HAP) | --- | --- | --- | [108] |
9. Discussion
10. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nuclide | t1/2 | Main Emissions | Energy (MeV) | Energy Recoil (KeV) | Range (µm) | Daughters | t1/2 | Decay | Energy (MeV) |
---|---|---|---|---|---|---|---|---|---|
227Th | 18.7 d | α | 6 | --- | 50–70 | 223Ra | |||
225Ac | 10 d | α | 5.8 | --- | 50–90 | 221Fr | 4.8 m | A | 7 |
γ | 0.218 | ||||||||
105 | 217At | 32.3 ms | A | 7 | |||||
116 | 213Bi | 45.6 m | A | 6 | |||||
β− | 0.444 | ||||||||
γ | 0.440 | ||||||||
132 | 213Po | 4.2 μs | A | 8 | |||||
209Tl | 2.2 m | β− | 0.659 | ||||||
160 | 209Pb | 3.5 h | β− | 0.198 | |||||
209Bi | Stable | --- | --- | ||||||
223Ra | 11.4 d | α | 5.7 | 108.4 | 50–70 | 219Ra | 3.96 s | A | 6.8 |
126 | 215Po | 1.78 ms | A | 7.4 | |||||
140 | 211Pb | 36.1 m | β− | --- | |||||
211Bi | 2.13 m | A | 6.6 | ||||||
β− | --- | ||||||||
211Po | 0.516 s | A | --- | ||||||
128 | 207Tl | 4.77 m | β− | --- | |||||
207Pb | Stable | --- | --- | ||||||
213Bi | 45.6 m | α | 6 | 50–90 | 132 | 213Po | 4.2 μs | A | 8 |
β− | 0.444 | 209Tl | 2.2 m | β− | 0.659 | ||||
γ | 0.440 | 209Pb | 3.5 h | β− | 0.198 | ||||
209Bi | Stable | --- | --- | ||||||
212Bi | 60.6 m | α | 6.1 | 40–100 | --- | 212Po | 0.3 µs | A | --- |
β− | 208Tl | 3.1 m | β− | --- | |||||
208Pb | Stable | --- | --- | ||||||
211At | 7.2 h | α | 5.9 | 55–80 | 116 | 207Bi | 33.4 y | β− | |
EC | 211Po | 0.516 s | A | --- | |||||
207Pb | Stable | --- | --- |
DOTA and Bifunctional Derivatives | Mainly Alpha Radionuclides | Ref | |
---|---|---|---|
DOTA: 1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetraacetic acid | | [32,36,37,38,39,40,41,42,43] | |
DOTAGA-anhydride | | 212Pb2+, 225Ac3+, 212/213Bi3+, 223Ra2+, 149Tb, 226/227Th | |
DOTA-NHS-ester | | ||
DOTAGA, R = amide, DOTA-NHS-ester | | ||
p-SCN-Bn-DOTA (C-DOTA) | | ||
DOTA derivatives TCMC, 3p-C-DEPA, and bifunctional derivatives | |||
3p-C-DEPA: 2-[(carboxymethyl)]-[5-(4-nitrophenyl-1-[4,7,10-tris-(carboxymethyl)- 1,4,7,10-tetraazacyclododecan-1-yl]pentan-2-yl)-amino]acetic acid | | [32,44,45,46,47] | |
3p-C-DEPA-NCS | | ||
TCMC, 1,4,7,10-tetrakis(carbamoylmethyl)- l,4,7,10-tetraazacyclododecane | | 212Pb2+,212/213Bi3+ | |
p-SCN-Bn-TCMC | | ||
NOTA, NETA, TACN-TM, and bifunctional derivatives | |||
NOTA: 1,4,7-triazacyclononane-1,4,7-triacetic acid | | [32,43,48] | |
p-SCN-Bn-NOTA (C-NOTA) | | ||
NETA: {4-[2-(bis-carboxymethylamino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}-acetic acid | | ||
C-NE3TA-NCS | | 212/213Bi3+, 212Pb2+ | |
3p-C-NETA | | ||
C-NETA-NCS | | ||
DTPA, bifunctional derivatives, and others | |||
DTPA: diethylenetriaminepentaacetic acid | | [5,32,36,41,42,49,50] | |
p-SCN-Bn-CHX-A″-DTPA | | ||
p-SCN-Bn-1B-DTPA | | ||
CHX-A”-DTPA, 2-(p-isothiocyanatobenzyl)- cyclohexyldiethylenetriaminepentaacetic acid | | 212/213Bi3+, 225Ac3+, 223Ra2+, 149Tb, 226/227Th | |
p-SCN-Bn-1B4M-DTPA | | ||
(Me-2,3-HOPO)4-Bn-NCS | | 226/227Th | |
HEHA, PEPA, and bifunctional derivatives | |||
HEHA: 1,4,7,10,13,16-hexaazacyclo-hexadecane-N′,N″,N‴,N,N⁗,N″″′-hexaacetic acid | | [32,36,37,38] | |
p-SCN-Bn-HEHA (C-HEHA) | | ||
PEPA: 1,4,7,10,13-pentaazacyclopentadecane-N,N′,N″,N‴,N⁗-pentaacetic acid | | ||
p-SCN-Bn-PEPA (C-PEPA) | | ||
MACROPA | | 225Ac3+ |
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Trujillo-Nolasco, M.; Morales-Avila, E.; Cruz-Nova, P.; Katti, K.V.; Ocampo-García, B. Nanoradiopharmaceuticals Based on Alpha Emitters: Recent Developments for Medical Applications. Pharmaceutics 2021, 13, 1123. https://doi.org/10.3390/pharmaceutics13081123
Trujillo-Nolasco M, Morales-Avila E, Cruz-Nova P, Katti KV, Ocampo-García B. Nanoradiopharmaceuticals Based on Alpha Emitters: Recent Developments for Medical Applications. Pharmaceutics. 2021; 13(8):1123. https://doi.org/10.3390/pharmaceutics13081123
Chicago/Turabian StyleTrujillo-Nolasco, Maydelid, Enrique Morales-Avila, Pedro Cruz-Nova, Kattesh V. Katti, and Blanca Ocampo-García. 2021. "Nanoradiopharmaceuticals Based on Alpha Emitters: Recent Developments for Medical Applications" Pharmaceutics 13, no. 8: 1123. https://doi.org/10.3390/pharmaceutics13081123