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Статті в журналах з теми "Targeted alpha therapy"

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Автор: Grafiati

Опубліковано: 4 червня 2021

Оновлено: 31 січня 2023

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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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Анотація:

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 recent studies demonstrating therapeutic applications of α-emitting labelled radiobioconjugates in targeted therapy. Finally, future prospects and the emerging possibility of therapeutic application of radiolabelled nanomaterials are discussed.

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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

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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16

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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17

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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18

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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Анотація:

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 TAT by macrodosimetry. The objective of this work is to review the microdosimetry of TAT as a function of the cell geometry, source-target configuration, cell sensitivity, and biological factors. A detailed knowledge of each of these parameters is required for accurate microdosimetric calculations.

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19

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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20

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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21

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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22

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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23

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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24

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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25

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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26

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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27

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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Анотація:

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 with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.

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28

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 detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

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29

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 successful treatment of the primary cancer. This review charts the developing role of systemic high LET in internal radiation therapy. Targeted alpha therapy is a rapidly advancing experimental therapy that holds promise to deliver high cytotoxicity to targeted cancer cells. Initially thought to be indicated for leukaemia and micrometastases, there is now evidence that solid tumours can also be regressed. Alpha therapy may be molecular or physiological in its targeting. Alpha emitting radioisotopes such as Bi-212, Bi-213, At-211 and Ac-225 are used to label monoclonal antibodies or proteins that target specific cancer cells. Alternatively, radium-233 is used for palliative therapy of breast and prostate cancers because of its bone seeking properties. In this review, preclinical studies and clinical trials of alpha therapy are discussed for leukaemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer, pancreatic cancer and other cancers. DOI: http://dx.doi.org/10.3329/bjmp.v6i1.19755 Bangladesh Journal of Medical Physics Vol.6 No.1 2013 21-38

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30

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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31

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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Анотація:

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 chromatographic, solution, and other techniques to isolate 212Pb from its parent radionuclide. Furthermore, molecules used for lead’s binding and radiochemical features of preparation and stability of compounds labeled with 212Pb are discussed. The results of preclinical studies with an estimation of therapeutic and tolerant doses as well as recently initiated clinical trials of targeted radiopharmaceuticals are presented.

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32

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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Анотація:

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; it is mainly excreted via the intestinal tract. 223Ra can be imaged in patients with a gamma camera. Dosimetry shows that, after a series of six treatments for a 70-kg person with an overall administered activity of 23 MBq, 223Ra results in an absorbed alpha dose of approximately 17 Gy to the bone endosteum and approximately 1.7 Gy to the red bone marrow. During administration, special care must be taken to ensure that no spill is present on the skin of either the patient or staff. Due to the low dose rate, the treatment is normally performed on an outpatient basis; the patient and carers should receive written instructions about the therapy and radiation protection.

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33

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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Анотація:

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 prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the α-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to date.

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34

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 targeted to tumors, can effectively kill cancer and limit bystander cytotoxicity. Macropa, an 18-member heterocyclic crown ether, can stably chelate Ac-225 at room temperature. Here, we synthesized and evaluated the efficacy of [225Ac]Ac–Macropa–GC33 in mice engrafted with the GPC3-expressing human liver cancer cell line HepG2. Following a pilot dose-finding study, mice (n = 10 per group) were treated with (1) PBS, (2) mass-equivalent unmodified GC33, (3) 18.5 kBq [225Ac]Ac–Macropa–IgG1 (isotype control), (4) 9.25 kBq [225Ac]Ac–Macropa–GC33, and (5) 18.5 kBq [225Ac]Ac–Macropa–GC33. While significant toxicity was observed in all groups receiving radioconjugates, the 9.25 kBq [225Ac]Ac–Macropa–GC33 group demonstrated a modest survival advantage compared to PBS (p = 0.0012) and 18.5 kBq [225Ac]Ac–IgG1 (p = 0.0412). Hematological analysis demonstrated a marked, rapid reduction in white blood cells in all radioconjugate-treated groups compared to the PBS and unmodified GC33 control groups. Our studies highlight a significant disadvantage of using directly-labeled biomolecules with long blood circulation times for TAT. Strategies to mitigate such treatment toxicity include dose fractionation, pretargeting, and using smaller targeting ligands.

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35

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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36

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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37

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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38

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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39

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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40

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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41

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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42

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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43

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 cancers using a variety of techniques, alpha emitters and MAbs. Observations from their cumulative experience suggest that TAT is safe and effectivebut needs further trials for practical acceptance. Especially critical is the issue of maximum tolerance dose (MTD) which needs to be established for maximum target kill. Bangladesh has the infrastructure to conduct aTAT clinical trial and can significantly add to the growing pool of data for advanced treatment of cancers through collaborative involvement in targeted alpha therapy research.Objective: The aim of the article is to present a general overview of targeted alpha therapy and to discuss the feasibility of a TAT clinical trial in Bangladesh in the context of current cancer management situation in the country.Method: Literature review of significant publications was done to obtain an update of the current status of targeted alpha therapy. Relevant issues of TAT are presented for a theoretical basis of the technology. Next, the methodology of a proposed clinical trial is discussed, together with the practicability of its introduction in Bangladesh.Conclusion: Implementation of TAT clinical trial will help to develop an advanced technology and build- up skilled manpower in Bangladesh.It will optimize the key parameters of targeted alpha therapy, i e stability and specific activity of the alpha-conjugate and establish the maximum tolerance dose for the AIC. If the clinical trial is successful, it can change the prognosis of many end-stage cancers. Patients in Bangladesh with advanced MUCI expressing tumors of the breast, ovary, pancreas and prostate can have some measure of hope with stability of the disease.Bangladesh J. Nuclear Med. 19(1): 43-50, January 2016

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Allen, Barry J., Syed M. Abbas Rizvi, Chang F. Qu, and Ross C. Smith. "Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer." Cancers 3, no. 2 (April 1, 2011): 1821–43. http://dx.doi.org/10.3390/cancers3021821.

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Washiyama, Kohshin. "Current Status of alpha emitters useful for targeted radionuclide therapy." Drug Delivery System 35, no. 2 (March 25, 2020): 102–13. http://dx.doi.org/10.2745/dds.35.102.

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Morgenstern, Alfred, Christos Apostolidis, Clemens Kratochwil, Mike Sathekge, Leszek Krolicki, and Frank Bruchertseifer. "An Overview of Targeted Alpha Therapy with 225Actinium and 213Bismuth." Current Radiopharmaceuticals 11, no. 3 (October 22, 2018): 200–208. http://dx.doi.org/10.2174/1874471011666180502104524.

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Grieve, Melyssa L., and Brett M. Paterson. "The Evolving Coordination Chemistry of Radiometals for Targeted Alpha Therapy." Australian Journal of Chemistry 75, no. 2 (December 7, 2021): 65–88. http://dx.doi.org/10.1071/ch21184.

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Several radiometals are of interest in the development of new α-emitting radiopharmaceuticals. This review highlights the role of coordination chemistry in the design of 225Ac, 212/213Bi, 212Pb, 149Tb, 227Th, and 223/224Ra radiopharmaceuticals to treat cancer. Several chelators have recently been developed that are addressing the specific requirements of each radiometal to provide outstanding radiolabelling and in vivo properties. These advances are supporting the momentum that is building around radiopharmaceuticals for targeted α therapy.

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Barry J, Allen. "Generic MUC1 Epitope for Targeted Alpha Therapy for Metastatic Cancer." Journal of Oncology Research 1, no. 1 (November 16, 2018): 1–11. http://dx.doi.org/10.31829/2637-6148/jor2018-1(1)-106.

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Jin, Yong Nan, Hye Kyung Chung, Joo Hyun Kang, Yong Jin Lee, Kwang Il Kimm, Young Joo Kim, Seunghoo Kim, and June-Key Chung. "Radioiodine Gene Therapy of Hepatocellular Carcinoma Targeted Human Alpha Fetoprotein." Cancer Biotherapy and Radiopharmaceuticals 23, no. 5 (October 2008): 551–60. http://dx.doi.org/10.1089/cbr.2008.0467.

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Corroyer-Dulmont, Aurélien, Samuel Valable, Nadia Falzone, Anne-Marie Frelin-Labalme, Ole Tietz, Jérôme Toutain, Manuel Sarmiento Soto, et al. "VCAM-1 targeted alpha-particle therapy for early brain metastases." Neuro-Oncology 22, no. 3 (September 20, 2019): 357–68. http://dx.doi.org/10.1093/neuonc/noz169.

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Abstract Background Brain metastases (BM) develop frequently in patients with breast cancer. Despite the use of external beam radiotherapy (EBRT), the average overall survival is short (6 months from diagnosis). The therapeutic challenge is to deliver molecularly targeted therapy at an early stage when relatively few metastatic tumor cells have invaded the brain. Vascular cell adhesion molecule 1 (VCAM-1), overexpressed by nearby endothelial cells during the early stages of BM development, is a promising target. The aim of this study was to investigate the therapeutic value of targeted alpha-particle radiotherapy, combining lead-212 (212Pb) with an anti–VCAM-1 antibody (212Pb-αVCAM-1). Methods Human breast carcinoma cells that metastasize to the brain, MDA-231-Br-GFP, were injected into the left cardiac ventricle of nude mice. Twenty-one days after injection, 212Pb-αVCAM-1 uptake in early BM was determined in a biodistribution study and systemic/brain toxicity was evaluated. Therapeutic efficacy was assessed using MR imaging and histology. Overall survival after 212Pb-αVCAM-1 treatment was compared with that observed after standard EBRT. Results 212Pb-αVCAM-1 was taken up into early BM with a tumor/healthy brain dose deposition ratio of 6 (5.52e108 and 0.92e108) disintegrations per gram of BM and healthy tissue, respectively. MRI analyses showed a statistically significant reduction in metastatic burden after 212Pb-αVCAM-1 treatment compared with EBRT (P < 0.001), translating to an increase in overall survival of 29% at 40 days post prescription (P < 0.01). No major toxicity was observed. Conclusions The present investigation demonstrates that 212Pb-αVCAM-1 specifically accumulates at sites of early BM causing tumor growth inhibition.

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