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1

HANAOKA, Hironari, and Tsutomu TAKEUCHI. "Interferon ^|^alpha;-targeted therapy." Japanese Journal of Clinical Immunology 36, no. 4 (2013): 181–88. http://dx.doi.org/10.2177/jsci.36.181.

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2

Zalutsky, M. R., and G. Vaidyanathan. "383 TARGETED ALPHA THERAPY." Radiotherapy and Oncology 102 (March 2012): S195. http://dx.doi.org/10.1016/s0167-8140(12)70332-8.

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3

Kozempel, Jan, and Martin Vlk. "Nanoconstructs in Targeted Alpha-Therapy." Recent Patents on Nanomedicine 4, no. 2 (March 11, 2015): 71–76. http://dx.doi.org/10.2174/1877912305666150102000549.

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4

Morgenstern, Alfred, Frank Bruchertseifer, and Christos Apostolidis. "Targeted Alpha Therapy with 213Bi." Current Radiopharmaceuticalse 4, no. 4 (October 1, 2011): 295–305. http://dx.doi.org/10.2174/1874471011104040295.

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5

Majkowska-Pilip, Agnieszka, Weronika Gawęda, Kinga Żelechowska-Matysiak, Kamil Wawrowicz, and Aleksander Bilewicz. "Nanoparticles in Targeted Alpha Therapy." Nanomaterials 10, no. 7 (July 13, 2020): 1366. http://dx.doi.org/10.3390/nano10071366.

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Recent advances in the field of nanotechnology application in nuclear medicine offer the promise of better therapeutic options. In recent years, increasing efforts have been made on developing nanoconstructs that can be used as carriers for immobilising alpha (α)-emitters in targeted drug delivery. In this publication, we provide a comprehensive overview of available information on functional nanomaterials for targeted alpha therapy. The first section describes why nanoconstructs are used for the synthesis of α-emitting radiopharmaceuticals. Next, we present the synthesis and summarise the rec
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6

Vaidyanathan, Ganesan, and Michael R. Zalutsky. "Targeted therapy using alpha emitters." Physics in Medicine and Biology 41, no. 10 (October 1, 1996): 1915–31. http://dx.doi.org/10.1088/0031-9155/41/10/005.

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7

Allen, Barry J., Chand Raja, Syed Rizvi, Yong Li, Wendy Tsui, David Zhang, Emma Song, et al. "Targeted alpha therapy for cancer." Physics in Medicine and Biology 49, no. 16 (July 31, 2004): 3703–12. http://dx.doi.org/10.1088/0031-9155/49/16/016.

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8

Sgouros, George. "Alpha-particles for targeted therapy." Advanced Drug Delivery Reviews 60, no. 12 (September 2008): 1402–6. http://dx.doi.org/10.1016/j.addr.2008.04.007.

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9

Morgenstern, A., K. Abbas, F. Bruchertseifer, and C. Apostolidis. "Production of Alpha Emitters for Targeted Alpha Therapy." Current Radiopharmaceuticalse 1, no. 3 (September 1, 2008): 135–43. http://dx.doi.org/10.2174/1874471010801030135.

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10

J. Allen, Barry. "Future Prospects for Targeted Alpha Therapy." Current Radiopharmaceuticalse 4, no. 4 (October 1, 2011): 336–42. http://dx.doi.org/10.2174/1874471011104040336.

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11

Frantellizzi, Viviana, Laura Cosma, Gabriele Brunotti, Arianna Pani, Angela Spanu, Susanna Nuvoli, Flaminia De Cristofaro, Liana Civitelli, and Giuseppe De Vincentis. "Targeted Alpha Therapy with Thorium-227." Cancer Biotherapy and Radiopharmaceuticals 35, no. 6 (August 1, 2020): 437–45. http://dx.doi.org/10.1089/cbr.2019.3105.

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12

Silindir-Gunay, Mine, Merve Karpuz, and A. Yekta Ozer. "Targeted Alpha Therapy and Nanocarrier Approach." Cancer Biotherapy and Radiopharmaceuticals 35, no. 6 (August 1, 2020): 446–58. http://dx.doi.org/10.1089/cbr.2019.3213.

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13

Guerra Liberal, Francisco D. C., Joe M. O'Sullivan, Stephen J. McMahon, and Kevin M. Prise. "Targeted Alpha Therapy: Current Clinical Applications." Cancer Biotherapy and Radiopharmaceuticals 35, no. 6 (August 1, 2020): 404–17. http://dx.doi.org/10.1089/cbr.2020.3576.

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14

Kim, Young-Seung, and Martin W. Brechbiel. "An overview of targeted alpha therapy." Tumor Biology 33, no. 3 (December 6, 2011): 573–90. http://dx.doi.org/10.1007/s13277-011-0286-y.

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15

Rahman, A. K. M. Rezaur, Mahathe Hasan Babu, Mustofa Khalid Ovi, Md Mahiuddin Zilani, Israt Sultana Eithu, and Amit Chakraborty. "Actinium-225 in Targeted Alpha Therapy." Journal of Medical Physics 49, no. 2 (April 2024): 137–47. http://dx.doi.org/10.4103/jmp.jmp_22_24.

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The utilization of actinium-225 (225Ac) radionuclides in targeted alpha therapy for cancer was initially outlined in 1993. Over the past two decades, substantial research has been conducted, encompassing the establishment of 225Ac production methods, various preclinical investigations, and several clinical studies. Currently, there is a growing number of compounds labeled with 225Ac that are being developed and tested in clinical trials. In response to the increasing demand for this nuclide, production facilities are either being built or have already been established. This article offers a co
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16

Allen, Barry J., Chand Raja, Syed Rizvi, Yong Li, Wendy Tsui, Peter Graham, John Thompson, et al. "Intralesional targeted alpha therapy for metastatic melanoma." Cancer Biology & Therapy 4, no. 12 (December 2005): 1318–24. http://dx.doi.org/10.4161/cbt.4.12.2251.

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17

Sattiraju, Anirudh, Kiran Kumar Solingapuram Sai, Ang Xuan, Darpan N. Pandya, Frankis G. Almaguel, Thaddeus J. Wadas, Denise M. Herpai, Waldemar Debinski, and Akiva Mintz. "IL13RA2 targeted alpha particle therapy against glioblastomas." Oncotarget 8, no. 26 (May 11, 2017): 42997–3007. http://dx.doi.org/10.18632/oncotarget.17792.

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18

HUANG, Chen-Yu, Susanna GUATELLI, Bradley M. OBORN, and Barry J. ALLEN. "Background Dose for Systemic Targeted Alpha Therapy." Progress in Nuclear Science and Technology 2 (October 1, 2011): 187–90. http://dx.doi.org/10.15669/pnst.2.187.

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19

Huang, Chen-Yu, Susanna Guatelli, Bradley M. Oborn, and Barry J. Allen. "Microdosimetry for Targeted Alpha Therapy of Cancer." Computational and Mathematical Methods in Medicine 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/153212.

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Targeted alpha therapy (TAT) has the advantage of delivering therapeutic doses to individual cancer cells while reducing the dose to normal tissues. TAT applications relate to hematologic malignancies and now extend to solid tumors. Results from several clinical trials have shown efficacy with limited toxicity. However, the dosimetry for the labeled alpha particle is challenging because of the heterogeneous antigen expression among cancer cells and the nature of short-range, high-LET alpha radiation. This paper demonstrates that it is inappropriate to investigate the therapeutic efficacy of TA
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20

Jurcic, Joseph G. "Targeted Alpha-Particle Therapy for Hematologic Malignancies." Seminars in Nuclear Medicine 50, no. 2 (March 2020): 152–61. http://dx.doi.org/10.1053/j.semnuclmed.2019.09.002.

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21

Allen, B. J., S. M. A. Rizvi, and Z. Tian. "Preclinical targeted alpha therapy for subcutaneous melanoma." Melanoma Research 11, no. 2 (April 2001): 175–82. http://dx.doi.org/10.1097/00008390-200104000-00013.

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22

Jurcic, Joseph G. "Targeted Alpha-Particle Therapy for Hematologic Malignancies." Journal of Medical Imaging and Radiation Sciences 50, no. 4 (December 2019): S53—S57. http://dx.doi.org/10.1016/j.jmir.2019.05.008.

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23

AL Darwish, Ruqaya, Alexander Hugo Staudacher, Eva Bezak, and Michael Paul Brown. "Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector." Computational and Mathematical Methods in Medicine 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/612580.

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There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix d
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24

Allen, Barry J. "Systemic Targeted Alpha Radiotherapy for Cancer - A Review." Bangladesh Journal of Medical Physics 6, no. 1 (July 31, 2014): 21–38. http://dx.doi.org/10.3329/bjmp.v6i1.19755.

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The fundamental principles of internal targeted alpha therapy for cancer were established many decades ago. The high linear energy transfer (LET) of alpha radiation to the targeted cancer cells causes double strand breaks in DNA. At the same time, the short range of alpha- radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and chemotherapy. Such therapies fail on several fronts, such as lack of control of some primary cancers (eg glioblastoma multiforme) and inhibition of the development of lethal metastatic cancer after success
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25

Müller, Cristina, Josefine Reber, Stephanie Haller, Holger Dorrer, Ulli Köster, Karl Johnston, Konstantin Zhernosekov, Andreas Türler, and Roger Schibli. "Folate Receptor Targeted Alpha-Therapy Using Terbium-149." Pharmaceuticals 7, no. 3 (March 13, 2014): 353–65. http://dx.doi.org/10.3390/ph7030353.

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26

Dahle, Jostein, and Roy Larsen. "Targeted Alpha-Particle Therapy with 227Th-Labeled Antibodies." Current Radiopharmaceuticalse 1, no. 3 (September 1, 2008): 209–14. http://dx.doi.org/10.2174/1874471010801030209.

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27

Allen, Barry. "Clinical Trials of Targeted Alpha Therapy for Cancer." Reviews on Recent Clinical Trials 3, no. 3 (September 1, 2008): 185–91. http://dx.doi.org/10.2174/157488708785700339.

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28

Miao, Y., M. Hylarides, T. Shelton, H. Moore, D. W. Wester, D. R. Fisher, A. Fritzberg, R. Testa, T. J. Hoffman, and T. P. Quinn. "289 Peptide-targeted alpha-radiation for melanoma therapy." European Journal of Cancer Supplements 2, no. 8 (September 2004): 88. http://dx.doi.org/10.1016/s1359-6349(04)80297-0.

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29

De Vincentis, G., W. Gerritsen, J. E. Gschwend, M. Hacker, V. Lewington, J. M. O’Sullivan, M. Oya, et al. "Advances in targeted alpha therapy for prostate cancer." Annals of Oncology 30, no. 11 (November 2019): 1728–39. http://dx.doi.org/10.1093/annonc/mdz270.

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30

Cai, Weibo, Zachary J. Kerner, Hao Hong, and Jiangtao Sun. "Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha." Biochemistry Insights 1 (January 2008): BCI.S901. http://dx.doi.org/10.4137/bci.s901.

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Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy wit
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31

Ocak, Meltem, and Levent Kabasakal. "Targeted Alpha Therapy - Promising Radionuclides Beyond Ac-225." Nuclear Medicine Seminars 9, no. 2 (September 1, 2023): 124–32. http://dx.doi.org/10.4274/nts.galenos.2023.0017.

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32

Ocak, Meltem, Ayfer Asiye Akit, and Perihan Ünak. "Targeted Alpha Radionuclide Therapy (TAT)-Ac-225 Radiopharmaceuticals." Nuclear Medicine Seminars 9, no. 1 (March 1, 2023): 16–24. http://dx.doi.org/10.4274/nts.galenos.2023.0003.

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33

Jang, Albert, Ayse T. Kendi, Geoffrey B. Johnson, Thorvardur R. Halfdanarson, and Oliver Sartor. "Targeted Alpha-Particle Therapy: A Review of Current Trials." International Journal of Molecular Sciences 24, no. 14 (July 19, 2023): 11626. http://dx.doi.org/10.3390/ijms241411626.

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Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (225actinium, 212lead, and 211astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase
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34

Yamamoto, S., T. Watabe, K. Kaneda-Nakashima, Y. Shirakami, K. Ooe, A. Toyoshima, T. Teramoto, A. Shinohara, and J. Hatazawa. "Development of GGAG alpha camera system for targeted alpha radionuclide therapy research." Journal of Instrumentation 16, no. 06 (June 1, 2021): P06009. http://dx.doi.org/10.1088/1748-0221/16/06/p06009.

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35

Kokov, Konstantin V., Bayirta V. Egorova, Marina N. German, Ilya D. Klabukov, Michael E. Krasheninnikov, Antonius A. Larkin-Kondrov, Kseniya A. Makoveeva, Michael V. Ovchinnikov, Maria V. Sidorova, and Dmitry Y. Chuvilin. "212Pb: Production Approaches and Targeted Therapy Applications." Pharmaceutics 14, no. 1 (January 13, 2022): 189. http://dx.doi.org/10.3390/pharmaceutics14010189.

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Over the last decade, targeted alpha therapy has demonstrated its high effectiveness in treating various oncological diseases. Lead-212, with a convenient half-life of 10.64 h, and daughter alpha-emitter short-lived 212Bi (T1/2 = 1 h), provides the possibility for the synthesis and purification of complex radiopharmaceuticals with minimum loss of radioactivity during preparation. As a benefit for clinical implementation, it can be milked from a radionuclide generator in different ways. The main approaches applied for these purposes are considered and described in this review, including chromat
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36

Lassmann, M., and U. Eberlein. "Targeted alpha-particle therapy: imaging, dosimetry, and radiation protection." Annals of the ICRP 47, no. 3-4 (April 17, 2018): 187–95. http://dx.doi.org/10.1177/0146645318756253.

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Systemic or locoregionally administered alpha-particle emitters are highly potent therapeutic agents used in oncology that are fundamentally novel in their mechanism and, most likely, overcome radiation resistance as the alpha particles emitted have a short range and a high linear energy transfer. The use of alpha emitters in a clinic environment requires extra measures with respect to imaging, dosimetry, and radiation protection. This is shown for the example of 223Ra dichloride therapy. After intravenous injection, 223Ra leaves the blood and is taken up rapidly in bone and bone metastases; i
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37

Tafreshi, Narges K., Michael L. Doligalski, Christopher J. Tichacek, Darpan N. Pandya, Mikalai M. Budzevich, Ghassan El-Haddad, Nikhil I. Khushalani, et al. "Development of Targeted Alpha Particle Therapy for Solid Tumors." Molecules 24, no. 23 (November 26, 2019): 4314. http://dx.doi.org/10.3390/molecules24234314.

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Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prosta
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38

Bell, Meghan M., Nicholas T. Gutsche, A. Paden King, Kwamena E. Baidoo, Olivia J. Kelada, Peter L. Choyke, and Freddy E. Escorcia. "Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma." Molecules 26, no. 1 (December 22, 2020): 4. http://dx.doi.org/10.3390/molecules26010004.

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Glypican-3 (GPC3) is expressed in 75% of hepatocellular carcinoma (HCC), but not normal liver, making it a promising HCC therapeutic target. GC33 is a full-length humanized monoclonal IgG1 specific to GPC3 that can localize to HCC in vivo. GC33 alone failed to demonstrate therapeutic efficacy when evaluated in patients with HCC; however, we posit that cytotoxic functionalization of the antibody with therapeutic radionuclides, may be warranted. Alpha particles, which are emitted by radioisotopes such as Actinium-225 (Ac-225) exhibit high linear energy transfer and short pathlength that, when ta
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39

Kozempel, J., M. Vlk, E. Málková, A. Bajzíková, J. Bárta, R. Santos-Oliveira, and A. Malta Rossi. "Prospective carriers of 223Ra for targeted alpha particle therapy." Journal of Radioanalytical and Nuclear Chemistry 304, no. 1 (September 19, 2014): 443–47. http://dx.doi.org/10.1007/s10967-014-3615-y.

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40

Morgenstern, Alfred, and Frank Bruchertseifer. "Development of Targeted Alpha Therapy from Bench to Bedside." Journal of Medical Imaging and Radiation Sciences 50, no. 4 (December 2019): S18—S20. http://dx.doi.org/10.1016/j.jmir.2019.06.046.

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41

Ferrier, Maryline G., and Valery Radchenko. "An Appendix of Radionuclides Used in Targeted Alpha Therapy." Journal of Medical Imaging and Radiation Sciences 50, no. 4 (December 2019): S58—S65. http://dx.doi.org/10.1016/j.jmir.2019.06.051.

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42

ALLEN, B. J., and N. BLAGOJEVIC. "Alpha- and beta-emitting radiolanthanides in targeted cancer therapy." Nuclear Medicine Communications 17, no. 1 (January 1996): 40–47. http://dx.doi.org/10.1097/00006231-199601000-00008.

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43

Molnar, I., E. Burak, J. Forbes, R. Simms, and J. Valliant. "The next generation of radioimmunotherapy: Targeted alpha therapy (TAT)." Annals of Oncology 29 (March 2018): iii6. http://dx.doi.org/10.1093/annonc/mdy046.020.

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44

Parker, Christopher, Valerie Lewington, Neal Shore, Clemens Kratochwil, Moshe Levy, Ola Lindén, Walter Noordzij, Jae Park, and Fred Saad. "Targeted Alpha Therapy, an Emerging Class of Cancer Agents." JAMA Oncology 4, no. 12 (December 1, 2018): 1765. http://dx.doi.org/10.1001/jamaoncol.2018.4044.

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45

Vranješ, S. D., M. Miederer, J. J. Čomor, D. Soloviev, and G. J. Beyer. "Labeling of antibodies with 149Tb for targeted alpha therapy." Journal of Labelled Compounds and Radiopharmaceuticals 44, S1 (May 2001): S718—S720. http://dx.doi.org/10.1002/jlcr.25804401253.

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46

Hurley, Kate, Meiyun Cao, Haiming Huang, and Yi Wang. "Targeted Alpha Therapy (TAT) with Single-Domain Antibodies (Nanobodies)." Cancers 15, no. 13 (July 4, 2023): 3493. http://dx.doi.org/10.3390/cancers15133493.

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The persistent threat of cancer necessitates the development of improved and more efficient therapeutic strategies that limit damage to healthy tissues. Targeted alpha therapy (TαT), a novel form of radioimmuno-therapy (RIT), utilizes a targeting vehicle, commonly antibodies, to deliver high-energy, but short-range, alpha-emitting particles specifically to cancer cells, thereby reducing toxicity to surrounding normal tissues. Although full-length antibodies are often employed as targeting vehicles for TαT, their high molecular weight and the presence of an Fc-region lead to a long blood half-l
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47

Bidkar, Anil P., Luann Zerefa, Surekha Yadav, Henry F. VanBrocklin, and Robert R. Flavell. "Actinium-225 targeted alpha particle therapy for prostate cancer." Theranostics 14, no. 7 (2024): 2969–92. http://dx.doi.org/10.7150/thno.96403.

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48

Takazoe, M., T. Tanaka, and J. Iwadare. "Targeted therapy for Crohn's disease (CD)-monoclonal antibody anti-TNF-.ALPHA. therapy." Nippon Daicho Komonbyo Gakkai Zasshi 56, no. 10 (2003): 841–48. http://dx.doi.org/10.3862/jcoloproctology.56.841.

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49

Nisa, Lutfun, Kamila Afroj Quadir, Shamim MF Begum, Raihan Hussain, and Mizanul Hasan. "Targeted Alpha Therapy Trial in Bangladesh: Promise for Advanced MUC1 – Expressing Tumors." Bangladesh Journal of Nuclear Medicine 19, no. 1 (March 4, 2018): 43–50. http://dx.doi.org/10.3329/bjnm.v19i1.35580.

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Introduction: Targeted alpha therapy (TAT) is a new experimental therapy that targets cancer cells and tumor capillary endothelial cells through intravenous injection of an alpha immuneconjugate (AIC). The AIC is formed by labeling the cancer targeting vector (monoclonal antibody) with alpha emitting radioisotopes using a bifunctionalchelator. The monoclonal antibody (MAb) is raised against antigens (e.g. MUC1) over-expressed on the surface of certain cancer cells. There are several centers notably in Europe, the US and Australia that are actively involved in TAT clinical trials of different c
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50

Einkauf, Jeffrey D., Luis H. Ortega, Sean M. McDeavitt, and Jonathan D. Burns. "Ion-Exchange Kinetics of Alpha-Zirconium Phosphate Nanoplatelets for Application in Targeted Alpha Therapy." Solvent Extraction and Ion Exchange 38, no. 6 (September 18, 2020): 612–28. http://dx.doi.org/10.1080/07366299.2020.1780699.

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