1932

Abstract

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease.

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2018-06-04
2024-12-11
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Literature Cited

  1. 1.  Schales F 1978. Brief history of Ra-224 usage in radiotherapy and radiobiology. Health Phys 35:25–32
    [Google Scholar]
  2. 2.  Macklis RM 1993. The great radium scandal. Sci Am 269:94–99
    [Google Scholar]
  3. 3.  Martland HS 1929. Occupational poisoning in manufacture of luminous watch dials—general review of hazard caused by ingestion of luminous paint, with especial reference to the New Jersey cases. J. Am. Med. Assoc. 92:466–73
    [Google Scholar]
  4. 4.  Baserga R, Yokoo H, Henegar GC 1960. Thorotrast-induced cancer in man. Cancer 13:1021–31
    [Google Scholar]
  5. 5.  Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM et al. 2013. Alpha emitter radium-223 and survival in metastatic prostate cancer. N. Engl. J. Med. 369:213–23
    [Google Scholar]
  6. 6.  Jurcic JG, Ravandi F, Pagel JM, Park JH, Smith BD et al. 2014. Phase I trial of targeted alpha-particle therapy using actinium-225 (225Ac)–lintuzumab (anti-CD33) in combination with low-dose cytarabine (LDAC) for older patients with untreated acute myeloid leukemia (AML). Blood 124:5293
    [Google Scholar]
  7. 7.  Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA et al. 2016. 225Ac-PSMA-617 for PSMA-targeted α-radiation therapy of metastatic castration-resistant prostate cancer. J. Nucl. Med. 57:1941–44
    [Google Scholar]
  8. 8.  Cordier D, Forrer F, Bruchertseifer F, Morgenstern A, Apostolidis C et al. 2010. Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial. Eur. J. Nucl. Med. Mol. Imaging 37:1335–44
    [Google Scholar]
  9. 9.  Sgouros G 2016. Radiobiology and Dosimetry for Radiopharmaceutical Therapy with Alpha-Particle Emitters Reston, VA: Soc. Nucl. Med. Mol. Imaging
    [Google Scholar]
  10. 10.  Barendsen GW, Koot CJ, van Kerson GR, Bewley DK, Field SB, Parnell CJ 1966. The effect of oxygen on the impairment of the proliferative capacity of human cells in culture by ionizing radiations of different LET. Int. J. Radiat. Biol. 10:317–27
    [Google Scholar]
  11. 11.  Barendsen GW, Walter HMD 1964. Effects of different ionizing radiations on human cells in tissue culture. 4. Modification of radiation damage. Radiat Res 21:314–29
    [Google Scholar]
  12. 12.  Barendsen GW 1964. Impairment of the proliferative capacity of human cells in culture by alpha-particles with differing linear-energy transfer. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 8:453–66
    [Google Scholar]
  13. 13.  Barendsen GW, Walter HMD, Bewley DK, Fowler JF 1963. Effects of different ionizing radiations on human cells in tissue culture. 3. Experiments with cyclotron-accelerated alpha-particles and deuterons. Radiat. Res 18:106–19
    [Google Scholar]
  14. 14.  Barendsen GW 1962. Dose-survival curves of human cells in tissue culture irradiated with alpha-, beta-, 20-KV. X- and 200-KV. X-radiation. Nature 193:1153–55
    [Google Scholar]
  15. 15.  Barendsen GW, Vergroesen AJ 1960. Irradiation of human cells in tissue culture with alpha-rays, beta-rays and X-rays. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 2:441
    [Google Scholar]
  16. 16.  Goodhead DT, Munson RJ, Thacker J, Cox R 1980. Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions. 4. Biophysical interpretation. Int. J. Radiat. Biol. 37:135–67
    [Google Scholar]
  17. 17.  Cox R, Masson WK 1979. Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions. 3. Human-diploid fibroblasts. Int. J. Radiat. Biol. 36:149–60
    [Google Scholar]
  18. 18.  Ballangrud ÅM, Yang WH, Charlton DE, McDevitt MR, Hamacher KA et al. 2001. Response of LNCaP spheroids after treatment with an alpha-particle emitter (213Bi)-labeled anti-prostate-specific membrane antigen antibody (J591). Cancer Res 61:2008–14
    [Google Scholar]
  19. 19.  Ballangrud ÅM, Yang WH, Hamacher KA, McDevitt MR, Ma D et al. 2000. Relative efficacy of the alpha-particle emitters Bi-213 and Ac-225 for radioimmunotherapy against micrometastases. Proceedings of the 41st Annual Meeting of the American Association for Cancer Research289 La Jolla: Univ. Calif.
    [Google Scholar]
  20. 20.  Barendsen GW, Beusker TLJ, Vergroesen AJ, Budke L 1960. Effect of different ionizing radiations on human cells in tissue culture. 2. Biol. Exp. Radiat. Res. 13:841–49
    [Google Scholar]
  21. 21.  Bloomer WD, McLaughlin WH, Neirinckx RD, Adelstein SJ, Gordon PR et al. 1981. Astatine-211–tellurium radiocolloid cures experimental malignant ascites. Science 212:340–41
    [Google Scholar]
  22. 22.  Humm JL 1987. A microdosimetric model of astatine-211 labeled antibodies for radioimmunotherapy. Int. J. Radiat. Oncol. Biol. Phys. 13:1767–73
    [Google Scholar]
  23. 23.  Humm JL, Chin LM 1993. A model of cell inactivation by alpha-particle internal emitters. Radiat. Res. 134:143–50
    [Google Scholar]
  24. 24.  Kassis AI, Harris CR, Adelstein SJ, Ruth TJ, Lambrecht R, Wolf AP 1986. The in vitro radiobiology of astatine-211 decay. Radiat. Res. 105:27–36
    [Google Scholar]
  25. 25.  Kozak RW, Atcher RW, Gansow OA, Friedman AM, Hines JJ, Waldmann TA 1986. Bismuth-212-labeled anti-Tac monoclonal-antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy. PNAS 83:474–78
    [Google Scholar]
  26. 26.  Kurtzman SH, Russo A, Mitchell JB, DeGraff W, Sindelar WF et al. 1988. Bismuth-212 linked to an antipancreatic carcinoma antibody: model for alpha-particle-emitter radioimmunotherapy. J. Natl. Cancer Inst. 80:449–52
    [Google Scholar]
  27. 27.  Macklis RM, Kinsey BM, Kassis AI, Ferrara JLM, Atcher RW et al. 1988. Radioimmunotherapy with alpha-particle-emitting immunoconjugates. Science 240:1024–26
    [Google Scholar]
  28. 28.  McDevitt MR, Ma D, Lai LT, Simon J, Borchardt P et al. 2001. Tumor therapy with targeted atomic nanogenerators. Science 294:1537–40
    [Google Scholar]
  29. 29.  Raju MR, Eisen Y, Carpenter S, Inkret WC 1991. Radiobiology of alpha-particles. 3. Cell inactivation by alpha-particle traversals of the cell nucleus. Radiat. Res. 128:204–9
    [Google Scholar]
  30. 30.  Sgouros G, Ballangrud ÅM, Jurcic JG, McDevitt MR, Humm JL et al. 1999. Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia. J. Nucl. Med. 40:1935–46
    [Google Scholar]
  31. 31.  Ballangrud ÅM, Yang WH, Palm S, Enmon R, Borchardt PE et al. 2004. Alpha-particle-emitting atomic generator (actinium-225)-labeled trastuzumab (Herceptin) targeting of breast cancer spheroids: efficacy versus HER2/neu expression. Clin. Cancer Res. 10:4489–97
    [Google Scholar]
  32. 32.  Song H, Hedayati M, Hobbs RF, Shao C, Bruchertseifer F et al. 2013. Targeting aberrant DNA double strand break repair in triple negative breast cancer with alpha particle emitter radiolabeled anti-EGFR antibody. Mol. Cancer Ther. 12:2043–54
    [Google Scholar]
  33. 33.  Bolch WE, Eckerman KF, Sgouros G, Thomas SR 2009. A generalized schema for radiopharmaceutical dosimetry—standardization of nomenclature. J. Nucl. Med. 50:477–84
    [Google Scholar]
  34. 34.  Hobbs RF, Song H, Huso DL, Sundel MH, Sgouros G 2012. A nephron-based model of the kidneys for macro-to-micro alpha-particle dosimetry. Phys. Med. Biol. 57:4403–24
    [Google Scholar]
  35. 35.  Hobbs RF, Song H, Watchman CJ, Bolch WE, Aksnes AK et al. 2012. A bone marrow toxicity model for 223Ra alpha-emitter radiopharmaceutical therapy. Phys. Med. Biol. 57:3207–22
    [Google Scholar]
  36. 36.  Sgouros G 2015. MIRD Monograph: Radiobiology and Dosimetry for Radiopharmaceutical Therapy with Alpha-Particle Emitters Reston, VA: Soc. Nucl. Med. Mol. Imaging
    [Google Scholar]
  37. 37.  Jurcic JG, McDevitt MR, Pandit-Taskar N, Divgi CR, Finn RD et al. 2006. Alpha-particle immunotherapy for acute myeloid leukemia (AML) with bismuth-213 and actinium-225. Cancer Biother. Radiopharm. 21:396
    [Google Scholar]
  38. 38.  Kratochwil C, Bruchertseifer F, Rathke H, Bronzel M, Apostolidis C et al. 2017. Targeted α therapy of mCRPC with 225actinium-PSMA-617: dosimetry estimate and empirical dose finding. J. Nucl. Med. 58:1624–31
    [Google Scholar]
  39. 39.  Corson DR, MacKenzie KR, Segr E 1940. Artificially radioactive element 85. Phys. Rev. 58:672–78
    [Google Scholar]
  40. 40.  Hauck ML, Larsen RH, Welsh PC, Zalutsky MR 1998. Cytotoxicity of alpha-particle-emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia. Br. J. Cancer 77:753–59
    [Google Scholar]
  41. 41.  Larsen RH, Akabani G, Welsh P, Zalutsky MR 1998. The cytotoxicity and microdosimetry of astatine-211-labeled chimeric monoclonal antibodies in human glioma and melanoma cells in vitro. Radiat. Res. 149:155–62
    [Google Scholar]
  42. 42.  Akabani G, Carlin S, Welsh P, Zalutsky MR 2006. In vitro cytotoxicity of 211At-labeled trastuzumab in human breast cancer cell lines: effect of specific activity and HER2 receptor heterogeneity on survival fraction. Nucl. Med. Biol. 33:333–47
    [Google Scholar]
  43. 43.  Petrich T, Korkmaz Z, Krull D, Frömke C, Meyer GJ, Knapp WH 2010. In vitro experimental 211At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin. Eur. J. Nucl. Med. Mol. Imaging 37:851–61
    [Google Scholar]
  44. 44.  Elgqvist J, Andersson H, Back T, Hultborn R, Jensen H et al. 2005. Therapeutic efficacy and tumor dose estimations in radioimmunotherapy of intraperitoneally growing OVCAR-3 cells in nude mice with At-211-labeled monoclonal antibody MX35. J. Nucl. Med. 46:1907–15
    [Google Scholar]
  45. 45.  Green DJ, Shadman M, Jones JC, Frayo SL, Kenoyer AL et al. 2015. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model. Blood 125:2111–19
    [Google Scholar]
  46. 46.  Burtner CR, Chandrasekaran D, Santos EB, Beard BC, Adair JE et al. 2015. 211Astatine-conjugated monoclonal CD45 antibody–based nonmyeloablative conditioning for stem cell gene therapy. Hum. Gene Ther. 26:399–406
    [Google Scholar]
  47. 47.  Kiess AP, Minn I, Vaidyanathan G, Hobbs RF, Josefsson A et al. 2016. (2S)-2-(3-(1-Carboxy-5-(4-211At-astatobenzamido)pentyl)ureido)-pentanedioic acid for PSMA-targeted alpha-particle radiopharmaceutical therapy. J. Nucl. Med. 57:1569–75
    [Google Scholar]
  48. 48.  Lyczko M, Pruszynski M, Majkowska-Pilip A, Lyczko K, Was B et al. 2017. 211At labeled substance P(5–11) as potential radiopharmaceutical for glioma treatment. Nucl. Med. Biol. 53:1–8
    [Google Scholar]
  49. 49.  Zalutsky MR, Reardon DA, Akabani G, Coleman RE, Friedman AH et al. 2008. Clinical experience with α-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6. J. Nucl. Med. 49:30–38
    [Google Scholar]
  50. 50.  Andersson H, Cederkrantz E, Bäck T, Divgi C, Elgqvist J et al. 2009. Intraperitoneal α-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of 211At-MX35 F(ab′)2—a phase I study. J. Nucl. Med. 50:1153–60
    [Google Scholar]
  51. 51.  Brechbiel MW, Pippin CG, McMury TJ, Milenic D, Roselli M et al. 1991. An effective chelating agent for labeling of monoclonal antibody with 212Bi for alpha-particle-mediated radioimmunotherapy. J. Chem. Soc. Chem. Commun. 17:1169–70
    [Google Scholar]
  52. 52.  Junghans RP, Dobbs D, Brechbiel MW, Mirzadeh S, Raubitschek AA et al. 1993. Pharmacokinetics and bioactivity of 1,4,7,10-tetra-azacylododecane N,N′,N′′,N′′′-tetraacetic acid (DOTA)-bismuth-conjugated anti-Tac antibody for α-emitter (212Bi) therapy. Cancer Res 53:5683–89
    [Google Scholar]
  53. 53.  Huneke RB, Pippin CG, Squire RA, Brechbiel MW, Gansow OA, Strand M 1992. Effective alpha-particle-mediated radioimmunotherapy of murine leukemia. Cancer Res 52:5818–20
    [Google Scholar]
  54. 54.  Hartmann F, Horak EM, Garmestani K, Wu C, Brechbiel MW et al. 1994. Radioimmunotherapy of nude mice bearing a human interleukin 2 receptor α–expressing lymphoma utilizing the α-emitting radionuclide–conjugated monoclonal antibody 212Bi-anti-Tac. Cancer Res 54:4362–70
    [Google Scholar]
  55. 55.  Rotmensch J, Whitlock JL, Schwartz JL, Hines JJ, Reba RC, Harper PV 1997. In vitro and in vivo studies on the development of the alpha-emitting radionuclide bismuth 212 for intraperitoneal use against microscopic ovarian carcinoma. Am. J. Obstet. Gynecol. 176:833–40
    [Google Scholar]
  56. 56.  Hassfjell SP, Bruland OS, Hoff P 1997. Bi-212-DOTMP: An alpha particle emitting bone-seeking agent for targeted radiotherapy. Nucl. Med. Biol. 24:231–37
    [Google Scholar]
  57. 57.  Jurcic JG, McDevitt MR, Sgouros G, Ballangrud ÅM, Finn RD et al. 1997. Targeted alpha-particle therapy for myeloid leukemias: a phase I trial of bismuth-213-HuM195 (anti-CD33). Blood 90:2245
    [Google Scholar]
  58. 58.  Kneifel S, Cordier D, Good S, Ionescu MCS, Ghaffari A et al. 2006. Local targeting of malignant gliomas by the diffusible peptidic vector 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid–substance P. Clin. Cancer Res. 12:3843–50
    [Google Scholar]
  59. 59.  Heeger S, Moldenhauer G, Egerer G, Wesch H, Martin S et al. 2003. Alpha-radioimmunotherapy of B-lineage non-Hodgkin's lymphoma using 213Bi-labelled anti-CD19-and anti-CD20-CHX-A-DTPA conjugates. Abstr. Pap. Am. Chem. Soc. 225:U261
    [Google Scholar]
  60. 60.  Raja C, Graham P, Rizvi S, Song E, Goldsmith H et al. 2007. Interim analysis of toxicity and response in phase 1 trial of systemic targeted alpha therapy for metastatic melanoma. Cancer Biol. Ther. 6:846–52
    [Google Scholar]
  61. 61.  Chappell LL, Dadachova E, Milenic DE, Garmestani K, Wu C, Brechbiel MW 2000. Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb. Nucl. Med. Biol. 27:93–100
    [Google Scholar]
  62. 62.  Meredith RF, Torgue J, Azure MT, Shen S, Saddekni S et al. 2014. Pharmacokinetics and imaging of Pb-212-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. Cancer Biother. Radiopharm. 29:12–17
    [Google Scholar]
  63. 63.  Meredith R, Torgue J, Shen S, Fisher DR, Banaga E et al. 2014. Dose escalation and dosimetry of first-in-human alpha radioimmunotherapy with Pb-212-TCMC-trastuzumab. J. Nucl. Med. 55:1636–42
    [Google Scholar]
  64. 64.  Zhang T, Zhu J, George DJ, Armstrong AJ 2015. Enzalutamide versus abiraterone acetate for the treatment of men with metastatic castration-resistant prostate cancer. Expert Opin. Pharmacother. 16:473–85
    [Google Scholar]
  65. 65.  Lorente D, Mateo J, Perez-Lopez R, de Bono JS, Attard G 2015. Sequencing of agents in castration-resistant prostate cancer. Lancet Oncol 16:e279–92
    [Google Scholar]
  66. 66.  Ramdahl T, Bonge-Hansen HT, Ryan OB, Larsen S, Herstad G et al. 2016. An efficient chelator for complexation of thorium-227. Bioorg. Med. Chem. Lett. 26:4318–21
    [Google Scholar]
  67. 67.  Dahle J, Borrebæk J, Melhus KB, Bruland ØS, Salberg G et al. 2006. Initial evaluation of 227Th-p-benzyl-DOTA-rituximab for low-dose rate α-particle radioimmunotherapy. Nucl. Med. Biol. 33:271–79
    [Google Scholar]
  68. 68.  Dahle J, Krogh C, Melhus KB, Borrebæk J, Larsen RH, Kvinnsland Y 2009. In vitro cytotoxicity of low-dose-rate radioimmunotherapy by the alpha-emitting radioimmunoconjugate thorium-227–DOTA–rituximab. Int. J. Radiat. Oncol. Biol. Phys. 75:886–95
    [Google Scholar]
  69. 69.  Abbas N, Heyerdahl H, Bruland ØS, Borrebæk J, Nesland J, Dahle J 2011. Experimental α-particle radioimmunotherapy of breast cancer using 227Th-labeled p-benzyl–DOTA–trastuzumab. EJNMMI Res 1:18
    [Google Scholar]
  70. 70.  Hagemann UB, Wickstroem K, Wang E, Shea AO, Sponheim K et al. 2016. In vitro and in vivo efficacy of a novel CD33-targeted thorium-227 conjugate for the treatment of acute myeloid leukemia. Mol. Cancer Ther. 15:2422–31
    [Google Scholar]
  71. 71.  Kaelin WG 2005. The concept of synthetic lethality in the context of anticancer therapy. Nat. Rev. Cancer 5:689–98
    [Google Scholar]
  72. 72.  McDevitt MR, Sgouros G, Finn RD, Humm JL, Jurcic JG et al. 1998. Radioimmunotherapy with alpha-emitting nuclides. Eur. J. Nucl. Med. 25:1341–51
    [Google Scholar]
  73. 73.  McDevitt MR, Finn RD, Sgouros G, Ma D, Scheinberg DA 1999. An 225Ac/213Bi generator system for therapeutic clinical applications: construction and operation. Appl. Radiat. Isot. 50:895–904
    [Google Scholar]
  74. 74.  McDevitt MR, Ma D, Simon J, Frank RK, Scheinberg DA 2002. Design and synthesis of 225Ac radioimmunopharmaceuticals. Appl. Radiat. Isot. 57:841–47
    [Google Scholar]
  75. 75.  Abou DS, Pickett J, Mattson JE, Thorek DLJ 2017. A radium-223 microgenerator from cyclotron-produced trace actinium-227. Appl. Radiat. Isot. 119:36–42
    [Google Scholar]
  76. 76.  Florimonte L, Dellavedova L, Maffioli LS 2016. Radium-223 dichloride in clinical practice: a review. Eur. J. Nucl. Med. Mol. Imaging 43:1896–909
    [Google Scholar]
  77. 77.  Lassmann M, Nosske D, Reiners C 2002. Therapy of ankylosing spondylitis with 224Ra-radium chloride: dosimetry and risk considerations. Radiat. Environ. Biophys. 41:173–78
    [Google Scholar]
  78. 78.  Jurcic JG, Caron PC, Nikula TK, Papadopoulos EB, Finn RD et al. 1995. Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias. Cancer Res 55:5908–10
    [Google Scholar]
  79. 79.  Jurcic JG, Larson SM, Sgouros G, McDevitt MR, Finn RD et al. 2002. Targeted alpha particle immunotherapy for myeloid leukemia. Blood 100:1233–39
    [Google Scholar]
  80. 80.  Rosenblat TL, McDevitt MR, Mulford DA, Pandit-Taskar N, Divgi CR et al. 2010. Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia. Clin. Can. Res. 16:5303–11
    [Google Scholar]
  81. 81.  Jurcic J, Levy M, Park J, Ravandi F, Perl A et al. 2017. Phase I trial of alpha-particle immunotherapy with 225Ac-lintuzumab and low-dose cytarabine in patients age 60 or older with untreated acute myeloid leukemia. J. Nucl. Med. 58:Suppl. 1456
    [Google Scholar]
  82. 82.  Jurcic JG, Ravandi F, Pagel JM, Park JH, Smith BD et al. 2015. Phase I trial of alpha-particle therapy with actinium-225 (Ac-225)–lintuzumab (anti-CD33) and low-dose cytarabine (LDAC) in older patients with untreated acute myeloid leukemia (AML). J. Clin. Oncol. 33:Suppl.7050
    [Google Scholar]
  83. 83.  Jurcic JG, Ravandi F, Pagel JM, Park JH, Smith BD et al. 2015. Phase I trial of targeted alpha-particle immunotherapy with 225Ac–lintuzumab (anti-CD33) and low-dose cytarabine (LDAC) in older patients with untreated acute myeloid leukemia (AML). Blood 126:3794
    [Google Scholar]
  84. 84.  Mauk MR, Gamble RC 1979. Preparation of lipid vesicles containing high levels of entrapped radioactive cations. Anal. Biochem. 94:302–7
    [Google Scholar]
  85. 85.  Henriksen G, Schoultz BW, Michaelsen TE, Bruland ØS, Larsen RH 2004. Sterically stabilized liposomes as a carrier for α-emitting radium and actinium radionuclides. Nucl. Med. Biol. 31:441–49
    [Google Scholar]
  86. 86.  Sofou S, Thomas JL, Lin H-Y, McDevitt MR, Scheinberg DA, Sgouros G 2004. Engineered liposomes for potential α-particle therapy of metastatic cancer. J. Nucl. Med. 45:253–60
    [Google Scholar]
  87. 87.  Chang M-Y, Seideman J, Sofou S 2008. Enhanced loading efficiency and retention of 225Ac in rigid liposomes for potential targeted therapy of micrometastases. Bioconjug. Chem. 19:1274–82
    [Google Scholar]
  88. 88.  Jurcic JG, Levy MY, Park JH, Ravandi F, Perl AE et al. 2016. Phase I trial of targeted alpha-particle therapy with actinium-225 (225Ac)–lintuzumab and low-dose cytarabine (LDAC) in patients age 60 or older with untreated acute myeloid leukemia (AML). Blood 128:4050
    [Google Scholar]
  89. 89.  Sofou S, Kappel BJ, Jaggi JS, McDevitt MR, Scheinberg DA, Sgouros G 2007. Enhanced retention of the α-particle-emitting daughters of actinium-225 by liposome carriers. Bioconjug. Chem. 18:2061–67
    [Google Scholar]
  90. 90.  Wang G, de Kruijff RM, Rol A, Thijssen L, Mendes E et al. 2014. Retention studies of recoiling daughter nuclides of 225Ac in polymer vesicles. Appl. Radiat. Isot. 85:45–53
    [Google Scholar]
  91. 91.  Sofou S, Enmon R, Palm S, Kappel B, Zanzonico P et al. 2010. Large anti-HER2/neu liposomes for potential targeted intraperitoneal therapy of micrometastatic cancer. J. Liposome Res. 20:330–40
    [Google Scholar]
  92. 92.  Sofou S 2008. Radionuclide carriers for targeting of cancer. Int. J. Nanomed. 3:181–99
    [Google Scholar]
  93. 93.  Gabizon AA 2001. PEGylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Cancer Investig 19:424–36
    [Google Scholar]
  94. 94.  Keizer RJ, Huitema ADR, Schellens JHM, Beijnen JH 2010. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin. Pharmacokinet. 49:493–507
    [Google Scholar]
  95. 95.  Harrington KJ, Rowlinson-Busza G, Syrigos KN, Abra RM, Uster PS et al. 2000. Influence of tumour size on uptake of 111In-DTPA-labelled PEGylated liposomes in a human tumour xenograft model. Br. J. Cancer 83:684–88
    [Google Scholar]
  96. 96.  Gabizon A, Papahadjopoulos D 1988. Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. PNAS 85:6949–53
    [Google Scholar]
  97. 97.  Palm S, Enmon RM, Matei C, Kolbert KS, Xu S et al. 2003. Pharmacokinetics and biodistribution of 86Y-trastuzumab for 90Y dosimetry in an ovarian carcinoma model: correlative microPET and MRI. J. Nucl. Med. 44:1148–55
    [Google Scholar]
  98. 98.  Lin YS, Nguyen C, Mendoza J-L, Escandon E, Fei D et al. 1999. Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor. J. Pharmacol. Exp. Ther. 288:371–78
    [Google Scholar]
  99. 99.  Nedrow JR, Josefsson A, Park S, Bäck T, Hobbs RF et al. 2017. Pharmacokinetics, microscale distribution, and dosimetry of alpha-emitter-labeled anti-PD-L1 antibodies in an immune competent transgenic breast cancer model. EJNMMI Res 7:57
    [Google Scholar]
  100. 100.  Woodward J, Kennel SJ, Stuckey A, Osborne D, Wall J et al. 2011. LaPO4 nanoparticles doped with actinium-225 that partially sequester daughter radionuclides. Bioconjug. Chem. 22:766–76
    [Google Scholar]
  101. 101.  McLaughlin MF, Woodward J, Boll RA, Wall JS, Rondinone AJ et al. 2013. Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy. PLOS ONE 8:e54531
    [Google Scholar]
  102. 102.  Piotrowska A, Leszczuk E, Bruchertseifer F, Morgenstern A, Bilewicz A 2013. Functionalized NaA nanozeolites labeled with Ra for targeted alpha therapy. J. Nanopart. Res. 15:2082
    [Google Scholar]
  103. 103.  Ruggiero A, Villa CH, Holland JP, Sprinkle SR, May C et al. 2010. Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes. Int. J. Nanomed. 5:783–802
    [Google Scholar]
  104. 104.  Bandekar A, Zhu C, Jindal R, Bruchertseifer F, Morgenstern A, Sofou S 2014. Anti-prostate-specific membrane antigen liposomes loaded with 225Ac for potential targeted antivascular alpha-particle therapy of cancer. J. Nucl. Med. 55:107–14
    [Google Scholar]
  105. 105.  Lingappa M, Song H, Thompson S, Bruchertseifer F, Morgenstern A, Sgouros G 2010. Immunoliposomal delivery of 213Bi for alpha-emitter targeting of metastatic breast cancer. Cancer Res 70:6815–23
    [Google Scholar]
  106. 106.  Mulvey JJ, Villa CH, McDevitt MR, Escorcia FE, Casey E, Scheinberg DA 2013. Self-assembly of carbon nanotubes and antibodies on tumours for targeted amplified delivery. Nat. Nanotechnol. 8:763–71
    [Google Scholar]
  107. 107.  Piotrowska A, Męczyńska-Wielgosz S, Majkowska-Pilip A, Koźmiński P, Wójciuk G et al. 2017. Nanozeolite bioconjugates labeled with 223Ra for targeted alpha therapy. Nucl. Med. Biol. 47:10–18
    [Google Scholar]
  108. 108.  Sattiraju A, Xiong X, Pandya DN, Wadas TJ, Xuan A et al. 2017. Alpha particle enhanced blood brain/tumor barrier permeabilization in glioblastomas using integrin alpha-v beta-v–targeted liposomes. Mol. Cancer Ther. 16:2191–200
    [Google Scholar]
  109. 109.  Rosenkranz AA, Vaidyanathan G, Pozzi OR, Lunin VG, Zalutsky MR, Sobolev AS 2008. Engineered modular recombinant transporters: application of new platform for targeted radiotherapeutic agents to α-particle emitting 211At. Int. J. Radiat. Oncol. Biol. Phys. 72:193–200
    [Google Scholar]
  110. 110.  Zhu C, Bandekar A, Sempkowski M, Banerjee SR, Pomper MG et al. 2016. Nanoconjugation of PSMA-targeting ligands enhances perinuclear localization and improves efficacy of delivered alpha-particle emitters against tumor endothelial analogues. Mol. Cancer Ther. 15:106–13
    [Google Scholar]
  111. 111.  Zhu X, Palmer MR, Makrigiorgos GM, Kassis AI 2010. Solid-tumor radionuclide therapy dosimetry: new paradigms in view of tumor microenvironment and angiogenesis. Med. Phys. 37:2974–84
    [Google Scholar]
  112. 112.  Zhu C, Sempkowski M, Holleran T, Linz T, Bertalan T et al. 2017. Alpha-particle radiotherapy: For large solid tumors diffusion trumps targeting. Biomaterials 130:67–75
    [Google Scholar]
  113. 113.  Estrella V, Chen T, Lloyd M, Wojtkowiak J, Cornnell HH et al. 2013. Acidity generated by the tumor microenvironment drives local invasion. Cancer Res 73:1524–35
    [Google Scholar]
  114. 114.  Cooks T, Schmidt M, Bittan H, Lazarov E, Arazi L et al. 2009. Local control of lung derived tumors by diffusing alpha-emitting atoms released from intratumoral wires loaded with radium-224. Int. J. Radiat. Oncol. Biol. Phys. 74:966–73
    [Google Scholar]
  115. 115.  Confino H, Hochman I, Efrati M, Schmidt M, Umansky V et al. 2015. Tumor ablation by intratumoral Ra-224-loaded wires induces anti-tumor immunity against experimental metastatic tumors. Cancer Immunol. Immunother. 64:191–99
    [Google Scholar]
  116. 116.  Ménager J, Gorin J-B, Maurel C, Drujont L, Gouard S et al. 2015. Combining α-radioimmunotherapy and adoptive T cell therapy to potentiate tumor destruction. PLOS ONE 10:e0130249
    [Google Scholar]
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