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Alpha Radionuclide Therapy

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Radiopharmaceuticals for Therapy

Abstract

Therapeutic applications of alpha (α)-emitting radionuclides were introduced soon after the isolation of radium from pitch blende by Marie Curie in the early twentieth century. Because of the very high linear energy transfer (LET), α-emitters can be very lethal and result in very effective cell killing sterilization if the α-decay commences at the cellular target site. With recent innovations in cancer cell targeting with antibodies and peptides and rapid targeting strategies, the efficacy of several radiopharmaceuticals to which α-emitters have been attached has been demonstrated. In particular, the effectiveness of pain management has recently demonstrated with 223Ra chloride (Xofigo®) in patients with hormone refractory skeletal metastases from prostate cancer. This chapter discusses various α-emitting radionuclides for therapy and several interesting applications.

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References

  • Abbas N, Heyerdahl H, Bruland OS, et al. Experimental α-particle radioimmunotherapy of breast cancer using 227Th-labeled p-benzyl-DOTA-trastuzumab. EJNMI Research. 2011. http://link.springer.com/article/10.1186/2191-219X-1-18/fulltext.html.

  • Abbas N, Bruland ØS, Brevik EM, et al. Preclinical evaluation of 227Th-labeled and 177Lu-labeled trastuzumab in mice with HER-2-positive ovarian cancer xenografts. Nucl Med Commun. 2012;33:838–47.

    Article  PubMed  CAS  Google Scholar 

  • Allen BJ. Future prospects for targeted alpha therapy. Curr Radiopharm. 2011;4(4):336–42.

    Article  PubMed  CAS  Google Scholar 

  • Apostolidis C, Molinet R, McGinley J, et al. Cyclotron production of Ac-225 for targeted alpha therapy. Appl Radiat Isot. 2005;62:383–7.

    Article  PubMed  CAS  Google Scholar 

  • Atcher RW, Friedman AM, Hines JJ. An improved generator for the production of 212Pb and 212Bi from Ra. Int J Rad Appl Instrum A. 1988;39:283–6.

    Article  PubMed  CAS  Google Scholar 

  • Azure MT, Archer RD, Sastry KSR, et al. Biological effect of lead-212 localized in the nucleus of mammalian cells: role of recoil energy in the radiotoxicity of internal alpha-particle emitters biological effect of lead-212 localized in the nucleus of mammalian cells: role of recoil energy in the radiotoxicity of internal alpha-particle emitters. Radiat Res. 1994;140:276–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bardiès M. Dosimetry and microdosimetry of targeted radiotherapy. Curr Pharm Des. 2000;6:1469–502.

    Article  PubMed  Google Scholar 

  • Barendsen GW, Koot CJ, Van Kersen GR, et al. The effect of oxygen on impairment of the proliferative capacity of human cells in culture by ionizing radiations of different LET. Int J Radiat Biol Relat Stud Phys Chem Med. 1966;10:317–27.

    Article  PubMed  CAS  Google Scholar 

  • Bertrand A, Legras B, Martin J. Use of radium-224 in the treatment of ankylosing spondylitis and rheumatoid synovitis. Health Phys. 1978;35:57–60.

    Article  PubMed  CAS  Google Scholar 

  • Beyer GJ, Comor J, Dakovic M, et al. Production routes of the alpha emitting 149Tb for medical application. Radiochim Acta. 2002;90:247–52.

    Article  CAS  Google Scholar 

  • Beyer GJ, Miederer M, Vranjes-Duric S, et al. Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab. Eur J Nucl Med Mol Imaging. 2004;31:547–54.

    Article  PubMed  CAS  Google Scholar 

  • Bolch WE, Eckerman KF, Sgouros G, et al. MIRD pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry-standardization of nomenclature. J Nucl Med. 2009;50:477–84.

    Article  PubMed  CAS  Google Scholar 

  • Boll RA, Malkemus D, Mirzadeh S. Production of actinium-225 for alpha particle mediated radioimmunotherapy. Appl Radiat Isot. 2005;62:667–79.

    Article  PubMed  CAS  Google Scholar 

  • Bomanji JB, Wong W, Gaze MN, Cassoni A, Waddington W, Solano J, Ell PJ. Treatment of neuroendocrine tumours in adults with 131I-MIBG therapy. Clin Oncol. 2003;15:193–8.

    Article  CAS  Google Scholar 

  • Brechbiel MW. Targeted alpha-therapy: past, present, future? Dalton Trans. 2007;2(43):4918–28.

    Article  CAS  Google Scholar 

  • Brown I, Carpenter RN. At a-particle radiotherapy for undifferentiated thyroid cancer. Acta Radiol Suppl. 1991;376:174–5.

    PubMed  CAS  Google Scholar 

  • Carlin S, Akabani G, Zalutsky MR. In vitro cytotoxicity of (211At)-astatide and (131)I-iodide to glioma tumor cells expressing the sodium/iodide symporter. J Nucl Med. 2003;44:1827.

    PubMed  CAS  Google Scholar 

  • Chappell LL, Deal KA, Dadachova E, et al. Synthesis, conjugation, and radiolabeling of a novel bifunctional chelating agent for 225Ac radioimmunotherapy applications. Bioconjug Chem. 2000;11:510–9.

    Article  PubMed  CAS  Google Scholar 

  • Chouin N, Bardies M. Alpha-particle microdosimetry. Curr Radiopharm. 2011;4(3):266–80.

    Article  PubMed  CAS  Google Scholar 

  • Dahle J, Borrebaek J, Melhus KB, et al. Initial evaluation of (227)Th-p-benzyl-DOTA-rituximab for low-dose rate alpha-particle radioimmunotherapy. Nucl Med Biol. 2006;33:271–9.

    Article  PubMed  CAS  Google Scholar 

  • Essler M, Gartner FC, Neff F, et al. Therapeutic efficacy and toxicity of 225Ac-labelled vs. 213Bi-labelled tumour-homing peptides in a preclinical mouse model of peritoneal carcinomatosis. Eur J Nucl Med Mol Imaging. 2012;39:602–12.

    Article  PubMed  CAS  Google Scholar 

  • Friesen C, Roscher M, Hormann I, et al. Anti-CD33-antibodies labelled with the alpha emitter Bismuth-213 kill CD33-positive acute myeloid leukaemia cells specifically by activation of caspases and break radio- and chemoresistance by inhibition of the anti-apoptotic proteins X-linked inhibitor of apoptosis protein and B-cell lymphoma-extra large. Eur J Cancer. 2013;49:2542–54.

    Article  PubMed  CAS  Google Scholar 

  • Goodhead DT. Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. Int J Radiat Biol. 1994;65:7–17.

    Article  PubMed  CAS  Google Scholar 

  • Hall EJ. Radiobiology for the radiologist. 4th ed. Philadelphia: JB Lippincott Company; 1994.

    Google Scholar 

  • Hauck ML, Larsen RH, Welsh PC, et al. Cytotoxicity of a-particle emitting 211At-labeled antibody in tumor spheroids: no effect of hyperthermia. Br J Cancer. 1998;77:753.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Henriksen G, Messelt S, Olsen E, Larsen RH. Optimization of cyclotron production parameters for the 209Bi(α,2n)211At reaction related to biomedical use of 211At. Appl Radiat Isot. 2001;54:829–34.

    Article  Google Scholar 

  • Heyerdahl H, Abbas N, Sponheim K, et al. Targeted alpha therapy with 227Th-trastuzumab of intraperitoneal ovarian cancer in nude mice. Curr Radiopharm. 2013;6(2):106–16.

    Article  PubMed  CAS  Google Scholar 

  • Holden CS, Schenter RE. Production of actinium-227 and thorium-228 from radium-226 to supply alpha-emitting isotopes radium-223, thorium-227, radium-224, bismuth-212. 2014.US 20140226774. http://www.google.com/patents/US20140226774.

  • Howell RW, Goddu SM, Narra VR, et al. Radiotoxicity of gadolinium-148 and radium-223 in mouse testes: relative biological effectiveness of alpha-particle emitters in vivo. Radiat Res. 1997;147:342–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Humm JL, Cobb LM. Nonuniformity of tumor dose in radioimmunotherapy. J Nucl Med. 1990;31:75–83.

    PubMed  CAS  Google Scholar 

  • IAEA Technical Report SeriEs 15. A basic toxicity classification of radionuclides. 1963. http://www.iaea.org/inis/collection/NCLCollectionStore/_Public/24/072/24072024.pdf.

  • IAEA Technical Report Series 468. Cyclotron produced radioisotopes: physical characteristics and production methods. 2009. http://www-pub.iaea.org/MTCD/publications/PDF/trs468_web.pdf.

  • Jurcic JG. Targeted alpha-particle immunotherapy with bismuth-213 and actinium-225 for acute myeloid leukemia. J Postgrad Med Edu Res. 2013;47(1):14–7.

    Article  Google Scholar 

  • Jurcic JG, Larson SM, Sgouros G, et al. Targeted alpha particle immunotherapy for myeloid leukemia. Blood. 2002;100:1233–9.

    PubMed  CAS  Google Scholar 

  • Kennel SJ, Mirzadeh S. Vascular targeted radioimmunotherapy with 213Bi – an alpha-particle emitter. Nucl Med Biol. 1998;25:241–6.

    Article  PubMed  CAS  Google Scholar 

  • Kennel SJ, Boll R, Stabin M, et al. Radioimmunotherapy of micrometastases in lung with vascular targeted 213Bi. Br J Cancer. 1999;80:175–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kennel SJ, Chappell LL, Dadachova K, et al. Evaluation of 225Ac for vascular targeted radioimmunotherapy of lung tumors. Cancer Biother Radiopharm. 2000;15:235–44.

    Article  PubMed  CAS  Google Scholar 

  • Koch L, Apostolidis C, Janssens W, et al. Production of Ac-225 and application of the Bi-213 daughter in cancer therapy. Czech J Phys. 1999;49:817–22.

    Article  CAS  Google Scholar 

  • Lebeda O, Jiran R, Rális J, et al. A new internal target system for production of 211At on the cyclotron U-120M. Appl Radiat Isot. 2005;63:49–53.

    Article  PubMed  CAS  Google Scholar 

  • Lorimore SA, Kadhim MA, Pocock DA, et al. Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation. Proc Natl Acad Sci U S A. 1998;95:5730–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lundh C, Lindencrona U, Schmitt A, et al. Biodistribution of free 211At and 125I- in nude mice bearing tumors derived from anaplastic thyroid carcinoma cell lines. Cancer Biother Radiopharm. 2006;21:591–600.

    Article  PubMed  CAS  Google Scholar 

  • Macklis RM. The great radium scandal. Sci Am. 1993;269:94–9.

    Article  PubMed  CAS  Google Scholar 

  • Metting NF, Palayoor ST, Macklis RM. Induction of mutations by bismuth-212 alpha particles at two genetic loci in human B-lymphoblasts. Radiat Res. 1992;132:339–45.

    Article  PubMed  CAS  Google Scholar 

  • Metzenbaum M. Radium: Its value in the treatment of lupus, rodent ulcer, and epithelioma, with reports of cases. Int Clin (JB Lippincott). 1905;4(14):21–31.

    Google Scholar 

  • Miederer M, Scheinberg DA, McDevitt MR. Realizing the potential of the Actinium-225 radionuclide generator in targeted alpha-particle therapy applications. Adv Drug Deliv Rev. 2008;60(12):1371–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Montavon G, Le Du A, Champion J, et al. DTPA complexation of bismuth in human blood serum. Dalton Tran. 2012;41(28):8615–23.

    Article  CAS  Google Scholar 

  • Mulford D, Scheinberg DA, Jurcic JG. The promise of targeted α-particle therapy. J Nucl Med. 2005;46(1):199S–204.

    PubMed  Google Scholar 

  • Murud KM, Larsen RH, Bruland OS, Hoff P. Influence of pretreatment with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APB) on organ uptake of 211At and I-labeled amidobisphosphonates in mice. Nucl Med Biol. 1999a;26:791–4.

    Article  PubMed  CAS  Google Scholar 

  • Murud KM, Larsen RH, Hoff P, et al. Synthesis, purification, and in vitro stability of 211At- and 125I-labeled amidobisphosphonates. Nucl Med Biol. 1999b;26:397–403.

    Article  PubMed  CAS  Google Scholar 

  • Nicolini M, Mazzi U. Therapeutic potential of alpha-emitters: chemistry to biology to clinical applications. Padova: SGE Editorali; 1999.

    Google Scholar 

  • Ning L, Jiannan J, Shangwu M, et al. Preparation and preliminary evaluation of astatine-211 labeled IgG via DTPA anhydride. J Radiol Nucl Chem. 1998;227:187–90.

    Article  Google Scholar 

  • Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  PubMed  CAS  Google Scholar 

  • Petrich T, Quintanilla-Martinez L, Korkmaz Z, et al. Effective cancer therapy with the alpha-particle emitter [211At]astatine in a mouse model of genetically modified sodium/iodide symporter-expressing tumors. Clin Cancer Res. 2006;15(12):1342–8.

    Article  CAS  Google Scholar 

  • Pouget JP, Mather SJ. General aspects of the cellular response to low- and high-LET radiation. Eur J Nucl Med. 2001;28:541–61.

    Article  PubMed  CAS  Google Scholar 

  • Proescher F. The intravenous injection of soluble radium salts in men. Radium. 1913;1:9–10.

    Google Scholar 

  • Rosenblat TL, McDevitt MR, Mulford DA, et al. Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia. Clin Cancer Res. 2010;16:5303–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schales F. Brief history of Ra-224 usage in radiotherapy and radiobiology. Health Phys. 1978;35:25–32.

    Article  CAS  Google Scholar 

  • Schwarz UP, Plascjak P, Beitzel MP, et al. Preparation of 211At labeled humanized anti-tac using 211At produced in disposable internal and external bismuth targets. Nucl Med Biol. 1998;25:89–93.

    Article  PubMed  CAS  Google Scholar 

  • Sgouros G, Finn RD, Humm JL. Radioimmunotherapy with alpha-emitting nuclides. Eur J Nucl Med. 1998;25(9):1341–51.

    Article  PubMed  Google Scholar 

  • Sgouros G, Roeske JC, McDevitt MR, et al. SNM MIRD Committee, Bolch WE, Brill AB, Fisher DR, Howell RW, Meredith RF, Sgouros G, Wessels BW, Zanzonico PB. MIRD Pamphlet No. 22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy. J Nucl Med. 2010;51:311–28.

    Google Scholar 

  • Sgouros G, Hobbs RF, Song H. Modelling and dosimetry for alpha-particle therapy. Curr Radiopharm. 2011;4(3):261–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Song H, Hobbs RF, Vajravelu R, et al. Radioimmunotherapy of breast cancer metastases with alpha-particle emitter 225Ac: comparing efficacy with 213Bi and 90Y. Cancer Res. 2009;69:8941–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vaidyanathan G, Zalutsky MR. Astatine radiopharmaceuticals: prospects and problems. Curr Radiopharm. 2008;1:177–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vaidyanathan G, Strickland DK, Zalutsky MR. Meta-[211At]astatobenzylguanidine: further evaluation of a potential therapeutic agent. Int J Cancer. 1994;15(57):908–13.

    Article  Google Scholar 

  • Vaidyanathan G, Affleck D, Welsh P, et al. Radioiodination and astatination of octreotide by conjugation labelling. Nucl Med Biol. 2000;27:329–37.

    Article  PubMed  CAS  Google Scholar 

  • Vaidyanathan G, Boskovitz A, Shankar S, et al. Radioiodine and 211At-labeled guanidinomethyl halobenzoyl octreotate conjugates: potential peptide radiotherapeutics for somatostatin receptor-positive cancers. Peptides. 2004;25(12):2087–97.

    Article  PubMed  CAS  Google Scholar 

  • Visser GWM, Diemer EL, Vo CM, et al. The biological behaviour of some organic astatine compounds in rats. Int J Appl Radiat Isot. 1981;32:913–7.

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Liu S, Zhang P, Zhang S, Naidu M, Wang Y. S-phase cells are more sensitive to high-linear energy transfer radiation. Int J Radiat Oncol Biol Phys. 2009;74:1236–41.

    Article  PubMed  CAS  Google Scholar 

  • Wessels BW, Rogus RD. Radionuclide selection and model absorbed dose calculations for radiolabeled tumor associated antigens. Med Phys. 1984;11:638–45.

    Article  PubMed  CAS  Google Scholar 

  • Zalutsky MR, Narula AS. Astatination of proteins using an N-succinimidyl tri-n-butylstannyl benzoate intermediate. Int J Rad Appl Instrum A. 1988;39:227–32.

    Article  PubMed  CAS  Google Scholar 

  • Zalutsky MR, Pruszynski M. Astatine-211 Production and availability. Curr Radiopharm. 2011;4:177–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zalutsky MR, Vaidyanathan G. Astatine-211-labeled radiotherapeutics: an emerging approach to targeted alpha-particle radiotherapy. Curr Pharm Des. 2000;6(14):1433–55.

    Article  PubMed  CAS  Google Scholar 

  • Zalutsky MR, Reardon DA, Akabani G, et al. Clinical experience with α-particle–emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6. J Nucl Med. 2008;49:30–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Nuclear Security and Isotope Division, Oak Ridge National Laboratory, OAK RIDGE, USA

    F. F. (Russ) Knapp

  2. Isotope Production and Applications Division, Bhabha Atomic Research Centre, Mumbai, India

    Ashutosh Dash

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Knapp, F.F.(., Dash, A. (2016). Alpha Radionuclide Therapy. In: Radiopharmaceuticals for Therapy . Springer, New Delhi. https://doi.org/10.1007/978-81-322-2607-9_3

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