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Re-emergence of the important role of radionuclide generators to provide diagnostic and therapeutic radionuclides to meet future research and clinical demands

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Abstract

Radionuclide generators have been the main stay of diagnostic nuclear medicine and it is no exaggeration to state that the growth of nuclear medicine would not have happened to the present levels but for the availability of 99Mo/99mTc generator. This article provides a brief account of the various radionuclide generators currently in clinical use or which have made substantial progress or likely to be materialized in the foreseeable future to bring evolutional progress in nuclear medicine. Further, a brief outline on the regulatory challenges and impact on radionuclide generator technology with the emergence of professionally run central radiopharmacies have been provided.

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References

  1. Knapp FF Jr, Baum RP (2012) Radionuclide generators—a new renaissance in the development of technologies to provide diagnostic and therapeutic radioisotopes for clinical applications. Curr Radiopharm 6(175–177):2012

    Google Scholar 

  2. Lambrecht RM (1983) Radionuclide generators. Radiochim Acta 34:9–24

    CAS  Google Scholar 

  3. Knapp FF Jr, Mirzadeh S (1994) The continuing important role of radionuclide generator systems for nuclear medicine. Eur J Nucl Med 21:1151–1165

    Google Scholar 

  4. Mirzadeh S, Knapp FF Jr (1996) Biomedical radioisotope generator systems. J Radioanal Nucl Chem 203:471–488

    CAS  Google Scholar 

  5. Knapp FF Jr, Butler TA (eds) (1984) In: Radionuclide generators: New systems for nuclear medicine applications, ACS Symposium Series 241. American Chemical Society, Washington, DC (USA)

    Google Scholar 

  6. Osso J, Knapp FF Jr (2011) In: Theobald T (ed) Sampson’s textbook on radiopharmacy, 4th edn. Pharmaceutical Press, London, pp 339–364

    Google Scholar 

  7. Roesch F, Knapp FF Jr (2003) In: Vertes A, Nagy S, Klencsar Z (eds) Handbook of nuclear and radiochemistry. Kluwer Academic Publishers, Amsterdam, pp 81–118

    Google Scholar 

  8. Chakravarty R, Dash A (2013) Development of radionuclide generators for biomedical applications. Lambert Academic Publishing GmbH & Co, Saarbrücken

    Google Scholar 

  9. Banerjee S, Pillai MRA, Ramamoorthy N (2001) Evolution of Tc-99m in diagnostic radiopharmaceuticals. Sem Nucl Med 31:260–277

    CAS  Google Scholar 

  10. IAEA (2008) 99mTechnetium radiopharmaceuticals: manufacture of kits. International Atomic Energy Agency (IAEA), Vienna, Austria. http://www-pub.iaea.org/MTCD/publications/PDF/trs466_web.pdf

  11. Eckelman WC (2009) Unparalleled contribution of technetium-99m to medicine over 5 decades. J Am Coll Cardiol Imaging 2:364–368

    Google Scholar 

  12. Chakravarty R, Dash A (2014) Nanomaterial based adsorbents: the prospect of developing new generation radionuclide generators to meet future research and clinical demands. J Radioanal Nucl Chem 299(1):741–775

    CAS  Google Scholar 

  13. Pillai MRA, Dash A, Knapp FF Jr (2012) Rhenium-188: availability from the 188W/188Re generator and status of current applications. Curr Radiopharm 4(3):228–243

    Google Scholar 

  14. Dash A, Knapp FF Jr, Pillai MRA (2013) 99Mo/99mTc separation: an assessment of technology options. Nucl Med Biol 40:67–176

    Google Scholar 

  15. Chakravarty R, Dash A, Pillai MRA (2012) Electrochemical separation is an attractive strategy for development of radionuclide generators for medical applications. Curr Radiopharm 4:271–287

    Google Scholar 

  16. Chakravarty R, Dash A, Pillai MRA (2012) Availability of yttrium-90 from strontium-90: a nuclear medicine perspective. Cancer Biother Radiopharm 27(10):621–641

    CAS  Google Scholar 

  17. Dash A, Chakravarty R (2014) Electrochemical separation: promises, opportunities, and challenges to develop radionuclide generators of next-generation to meet clinical demands. Ind Eng Chem Res 53(10):3766–3777

    CAS  Google Scholar 

  18. IAEA (2009) Therapeutic Radionuclide Generators: 90Sr/90Y and 188W/188Re generators. IAEA Technical Report Series No. 470, International Atomic Energy Agency (IAEA), Vienna, Austria. http://www-pub.iaea.org/MTCD/publications/PDF/trs470_web.pdf

  19. Rösch F, Baum RP (2011) Generator-based PET radiopharmaceuticals for molecular imaging of tumours: on the way to theranostics. Dalton Trans 21(40):6104–6111

    Google Scholar 

  20. Rösch F, Baum RP (eds) (2013) Theranostics, gallium-68, and other radionuclides: a pathway to personalized diagnosis and treatment, recent results in cancer research, vol 194. Springer, New York

    Google Scholar 

  21. IAEA (2010) Production of long lived parent radionuclides for generators: 68Ge, 82Sr, 90Sr and 188W, IAEA Radioisotopes and Radiopharmaceuticals Technical Report Series No. 2, International Atomic Energy Agency (IAEA), Vienna, Austria. http://www-pub.iaea.org/MTCD/publications/PDF/Pub1436_web.pdf

  22. Dash A, Knapp FF Jr, Pillai MRA (2013) Industrial radionuclide generators: a potential step towards accelerating radiotracer investigations in industry. RSC Adv 3:14890–14909

    CAS  Google Scholar 

  23. Pillai MRA, Dash A, Knapp FF Jr (2013) Sustained availability of technetium-99m—possible paths forward. J Nucl Med 54:313–323

    CAS  Google Scholar 

  24. Colombetti LG LG (1969) Experience with purity tests of 113Sn/113mIn generators. Int J Appl Radiat Isot 20(10):717–724

    Google Scholar 

  25. Subramanian G, McAfee JG (1967) A radioisotope generator of indium-113m. Int J Appl Radiat Isot 18:215–221

    CAS  Google Scholar 

  26. Hnatowich DJ (1977) A review of radiopharmaceutical development with short-lived generator-produced radionuclides other than 99mTc. Int J Appl Radiat Isot 28:169–181

    CAS  Google Scholar 

  27. Lin T, Tsai Z, Luan C (1982) Preparation of 113mIn-generator from enriched 112Sn metal. Int J Appl Radiat Isot 33(9):745–749

    CAS  Google Scholar 

  28. Breeman WA, de Blois E, Sze Chan H, Konijnenberg M, Kwekkeboom DJ, Krenning EP (2011) 68Ga-labeled DOTA-peptides and 68Ga-labeled radiopharmaceuticals for positron emission tomography: current status of research, clinical applications, and future perspectives. Sem Nucl Med 41(4):314–321

    Google Scholar 

  29. Smith DL, Breeman WA, Sims-Mourtada J (2013) The untapped potential of gallium 68-PET: the next wave of 68Ga-agents. Appl Radiat Isot 76:14–23

    CAS  Google Scholar 

  30. Banerjee SR, Pomper MP (2013) Clinical applications of gallium-68. Appl Radiat Isot 76:2–13

    CAS  Google Scholar 

  31. Decristoforo C (2012) Gallium-68—a new opportunity for PET available from a long shelf life generator—automation and applications. Curr Radiopharm 5:212–220

    CAS  Google Scholar 

  32. Ambrosini V, Campana D, Tomassetti P, Fanti S (2012) 68Ga-labelled peptides for diagnosis of gastroenteropancreatic NET. Eur J Nucl Med Mol Imaging 39:S52–S60

    Google Scholar 

  33. Rice SL, Roney CA, Daumar P, Lewis JS (2011) The next generation of positron emission tomography radiopharmaceuticals in oncology. Semin Nucl Med 41:265–282

    Google Scholar 

  34. Rosch F (2013) 68Ge/68Ga generators: past, present, and future. Rec Res, Cancer Res 194:3–16

    CAS  Google Scholar 

  35. Rosch F (2013) Past, present, and future of 68Ge/68Ga generators. Appl Radiat Isot 76:24–30

    CAS  Google Scholar 

  36. Breeman WA, Verbruggen AM (2007) The 68Ge/68Ga generator has high potential, but when can we use 68Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging 34:978–981

    Google Scholar 

  37. Smith DL, Breeman WA, Sims-Mourtada J (2013) The untapped potential of gallium 68-PET: the next wave of 68Ga-agents. Appl Radiat Isot 76:14–23

    CAS  Google Scholar 

  38. Roesch F, Riss PJ (2010) The renaissance of the 68Ge/68Ga radionuclide generator initiates new developments in 68Ga radiopharmaceutical chemistry. Curr Top Med Chem 10:1633–1668

    CAS  Google Scholar 

  39. Velikyan I (2014) Prospective of 68Ga-radiopharmaceutical development. Theranostics. 4(1):47–80

    CAS  Google Scholar 

  40. IGG100 68Ge/68Ga Generator Product Information by Eckert & Ziegler AG, Berlin, Germany. http://www.radiustech.it/public/files/1d000044.pdf

  41. Mukherjee A, Pandey U, Chakravarty R, Sarma HD, Dash A (2014) Development of single vial kits for preparation of 68Ga-labelled peptides for PET imaging of neuroendocrine tumours. Mol Imaging Biol 16(4):550–557

    Google Scholar 

  42. Yang BY, Jeong JM, Kim YJ, Choi JY, Lee YS, Lee DS, Chung JK, Lee MC (2010) Formulation of 68Ga BAPEN kit for myocardial positron emission tomography imaging and biodistribution study. Nucl Med Biol 37:149–155

    CAS  Google Scholar 

  43. Wängler C, Wängler B, Lehner S, Elsner A, Todica A, Bartenstein P, Hacker M, Schirrmacher R (2011) A universally applicable 68Ga labeling technique for proteins. J Nucl Med 52:586–591

    Google Scholar 

  44. Loktionova N, Filosofov D, Pruszynski M, Rösch F (2010) Design and performance of a novel 5 mCi 44Ti/44Sc radionuclide generator. J Nucl Med 51(Suppl 2):590

    Google Scholar 

  45. Filosofov DV, Loktionova NS, Rösch F (2010) A 44Ti/44Sc radionuclide generator for potential application of 44Sc-based PET-radiopharmaceuticals. Radiochimi Acta 98(3):149–156

    CAS  Google Scholar 

  46. Roesch F (2012) Scandium-44: benefits of a long-lived PET radionuclide available from the 44Ti/44Sc generator system. Curr Radiopharm 4(3):187–201

    Google Scholar 

  47. Pruszyński M, Loktionova NS, Filosofov DV, Rösch F (2010) Post-elution processing of 44Ti/44Sc generator-derived 44Sc for clinical application. Appl Radiat Isot 68(9):1636–1641

    Google Scholar 

  48. Hoehr C, Oehlke E, Benard F, Lee CJ, Hou X, Badesso B, Ferguson S, Miao Q, Yang H, Buckley K, Hanemaayer V, Zeisler S, Ruth T, Celler A, Schaffer P (2014) 44gSc production using a water target on a 13 MeV cyclotron. Nucl Med Biol 41(5):401–406

    CAS  Google Scholar 

  49. Severin GW, Engle JW, Valdovinos HF, Barnhart TE, Nickles RJ (2012) Cyclotron produced 44gSc from natural calcium. Appl Radiat Isot 70(8):1526–1530

    CAS  Google Scholar 

  50. Ejnisman R, Goldman ID, Pascholati PR, da Cruz MT, Oliveira RM, Norman EB, Zlimen II, Wietfeldt FE, Larimer RM, Chan YD, Lesko KT, García A (1996) Cross sections for 45Sc(p,2n)44Ti and related reactions. Phys Rev C: Nucl Phys 54(4):2047–2050

    CAS  Google Scholar 

  51. Müller C, Bunka M, Reber J, Fischer C, Zhernosekov K, Türler A, Schibli R (2013) Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent β-emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate. J Nucl Med 54(12):2168–2174

    Google Scholar 

  52. Muller C (2013) Folate-based radiotracers for PET imaging—update and perspective. Molecules 18:5005–5031

    CAS  Google Scholar 

  53. Pruszyński M, Majkowska-Pilip A, Loktionova NS, Eppard E, Roesch F (2012) Radiolabeling of DOTATOC with the long-lived positron emitter 44Sc. Appl Radiat Isot 70:974–979

    Google Scholar 

  54. Müller C, Bunka M, Reber J, Fischer C, Zhernosekov K, Türler A, Schibli R (2013) Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent β-emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate. J Nucl Med 54:2168–7214

    Google Scholar 

  55. Majkowska-Pilip A, Bilewicz A (2011) Macrocyclic complexes of scandium radionuclides as precursors for diagnostic and therapeutic radiopharmaceuticals. J Inorg Biochem 105:313–320

    CAS  Google Scholar 

  56. Mcgee T, Rao CL, Saha GB, Yaffe L (1970) Nuclear interactions of Sc-45 and Zn-68 with protons of medium energy. Nucl Phys A 150:11

    CAS  Google Scholar 

  57. Sajjad M, Lambrecht RM (1986) Separation of tracer titanium-44 from vanadium. Anal Chem 58:667–668

    CAS  Google Scholar 

  58. IAEA (2009) Cyclotron produced radionuclides: physical characteristics and production methods. IAEA Technical Report Series 468, International Atomic Energy Agency (IAEA), Vienna, Austria. http://www-pub.iaea.org/MTCD/publications/PubDetails.asp?pubId=7892

  59. Robinson GD, F Zielinski FW, Lee AW (1980) The zinc-62/copper-62 generator: a convenient source of copper-62 for radiopharmaceuticals. Int J Radiat Isot 31:111–116

    CAS  Google Scholar 

  60. Fujibayashi Y, Matsumoto K, Yonekura Y, Konishi J, Yokoyama A (1989) A new zinc-62/copper-62 generator as a copper-62 source for PET radiopharmaceuticals. J Nucl Med 30:1838–1842

    CAS  Google Scholar 

  61. Mathias CJ, Margenau WH, Brodack JW, Welch MJ, Green MA (1991) A remote system for the synthesis of copper-62 labeled Cu(PTSM). Int J Rad Appl Instrum A 42:317–320

    CAS  Google Scholar 

  62. Dash A, Knapp FF Jr, Pillai MRA (2013) Targeted radionuclide therapy—an overview. Curr Radiopharm 6:152–180

    CAS  Google Scholar 

  63. Edelman MJ, Clamon G, Kahn D, Magram M, Lister-James J, Line BR (2009) Targeted radiopharmaceutical therapy for advanced lung cancer—Phase I trial of rhenium-188 Re-188 P2045, a somatostatin analog. J Thorac Oncol. 4(12):1550–1554

    Google Scholar 

  64. Jeong JM, Knapp FF Jr (2008) Use of the ORNL tungsten-188/rhenium-188 generator for preparation of rhenium-188 HDD/and AHDD/lipiodol complexes for transarterial liver cancer therapy. Semin Nucl Med 38(2):S19–S29

    Google Scholar 

  65. Argyrou M, Valassi A, Andreou M, Lyra M (2013) Rhenium-188 production in hospitals, by w-188/re-188 generator, for easy use in radionuclide therapy. Int J Mol Imaging 2013:290750. doi:10.1155/2013/290750

    Google Scholar 

  66. Knapp FF Jr, Turner JH, Jeong JM, Padhy AK (2004) Issues associated with the use of the tungsten-188/rhenium-188 generator and concentration system and preparation of Re-188-HDD. World J Nucl Med 3:137–143

    Google Scholar 

  67. Knapp FF Jr, Beets AL, Guhlke S, Zamora PO, Bender H, Palmedo H, Biersack HJ (1997) Availability of rhenium-188 from the alumina-based tungsten-188/rhenium-188 generator for preparation of rhenium-188-labeled radiopharmaceuticals for cancer treatment. Anticancer Res 17:1783–1795

    CAS  Google Scholar 

  68. Callahan AP, Rice DE, Knapp FF Jr (1989) Rhenium-188 for therapeutic applications from an alumina-based tungsten-188/rhenium-188 generator. Nucl. Compact 20:3–6

    CAS  Google Scholar 

  69. Knapp FF Jr, Lisic EC, Mirzadeh S, Callahan AP (1994) Tungsten-188/carrier-free rhenium-188 perrhenic acid generator system. U.S. Patent No. 5,186,913, Issued 4 Jan 1994

  70. Knapp FF Jr, Callahan AP, Beets AL, Mirzadeh S S (1994) Processing of reactor-produced 188W for fabrication of clinical scale alumina based 188W/188Re Generators. Appl Radiat Isot 45:1123–1128

    CAS  Google Scholar 

  71. Abram U, Alberto R (2006) Technetium and rhenium—coordination chemistry and nuclear medical applications. J Braz Chem Soc 17:1486–1500

    CAS  Google Scholar 

  72. Savio E, Gaudiano J, Robles AM, Balter H, Paolino A, López A, Hermida JC, De Marco E, Martinez G, Osinaga E, Knapp FF Jr (2001) Rhenium-188 HEDP: pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose. BMC Nucl Med 1:2–10

    Google Scholar 

  73. Blower PJ, Kettle AG, O’Doherty MJ, Coakley AJ, Knapp FF Jr (2000) 99mTc(V)-DMSA quantitatively predicts 188Re(V) DMSA distribution in patients with prostate cancer metastatic to bone. Eur J Nucl Med 9:1405–1409

    Google Scholar 

  74. Liepe K, Hlises R, Kropp J, Gruning T, Runge R, Koch R, Knapp FF Jr, Franke WG (2000) Rhenium-188-HEDP in palliative treatment of bone metastases. Cancer Biother Radiopharm 15:261–265

    CAS  Google Scholar 

  75. Palmedo H, Guhlke S, Bender H, Sartor J, Schoeneich G, Grunwald F, Knapp FF Jr, Biersack HJ (2000) Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. Eur J Nucl Med 27:123–130

    CAS  Google Scholar 

  76. Knapp FF Jr, Spencer R, Kropp J (2001) Intravascular radiation therapy with radioactive filled balloons for inhibition of restenosis after angioplasty: a new opportunity for nuclear medicine. J Nucl Med 42:1384–1387

    CAS  Google Scholar 

  77. Weinberger J, Giedd KN, Simon AD, Marboe C, Knapp FF Jr, Trichter F, Amols H (1999) Radioactive beta-emitting solution filled balloon treatment prevents porcine coronary restonosis. Cardiovasc Radiat Med 1:252–256

    CAS  Google Scholar 

  78. Tzanopoulou S, Sagnou M, Paravatou-Petsotas M, Gourni E, Loudos G, Xanthopoulos S, Lafkas D, Kiaris H, Varvarigou A, Pirmettis IC, Papadopoulos M, Pelecanou M (2010) Evaluation of Re and 99mTc complexes of 2-(4′-aminophenyl) benzothiazole as potential breast cancer radiopharmaceuticals. J Med Chem 53:4633–4641

    CAS  Google Scholar 

  79. Chen Y, Xiong QF, Yang XQ, He L, Huang ZW (2010) Evaluation of 188Re-DTPA-deoxyglucose as a potential cancer radiopharmaceutical. AJR Am J Roentgenol 194(3):761–765

    Google Scholar 

  80. Jeong JM, Lee YJ, Kim EH, Chang YS, Kim YJ, Son M, Lee DS, Chung JK, Lee MC (2003) Preparation of 188Re-labeled paper for treating skin cancer. Appl Radiat Isot 58(5):551–555

    CAS  Google Scholar 

  81. Chakravarty R, Pandey U, Manolkar RB, Dash A, Venkatesh M, Pillai MRA (2008) Development of an electrochemical 90Sr/90Y generator for the separation of 90Y suitable for targeted therapy. Nucl Med Biol 35:245–252

    CAS  Google Scholar 

  82. Isotope Technologies Dresde (2010) Kamadhenu electrochemical 90Sr/90Y generator, model KA 01 operating manual. Isotope Technologies Dresden, Germany. http://www.itd-dresden.de/index.php?article_id=78

  83. Chakraborty S, Chakravarty R, Sarma HD, Pillai MRA, Dash A (2014) Utilization of a novel electrochemical 90Sr/90Y generator for the preparation of 90Y-labeled RGD peptide dimer in clinically relevant dose. Radiochim Acta 102(6):523–534

    CAS  Google Scholar 

  84. Dash A, Chakravarty R (2014) Pivotal role of separation chemistry in the development of radionuclide generators to meet clinical demands. RSC Adv 4:42779–42803

    CAS  Google Scholar 

  85. Pandey U, Dhami PS, Jagesia P, Venkatesh M, Pillai MRA (2008) Extraction paper chromatography technique for the radionuclide purity evaluation of 90Y for clinical use. Anal Chem 80:801–807

    CAS  Google Scholar 

  86. Pandey U, Kumar Y, Dash A (2013) Validation of an extraction paper chromatography (EPC) technique for estimation of trace levels of 90Sr in 90Y solutions obtained from 90Sr/90Y generator systems. J Radioanal Nucl Chem 300(1):355–360

    Google Scholar 

  87. Pandey U, Gamre N, Chakravarty R, Pillai MRA, Dash A Investigation on the influence of metal ion impurities on the complexation behavior of generator produced 90Y with different bifunctional chelators. Radiochim Acta. doi:10.1515/ract-2013-2190 (in press)

  88. Morgenstern A, Bruchertseifer F, Apostolidis C (2011) Targeted alpha therapy with 213Bi. Curr Radiopharm 4:295–305

    CAS  Google Scholar 

  89. Brechbiel MW (2007) Targeted alpha-therapy: past, present, future? Dalton Trans 21:4918–4928

    Google Scholar 

  90. Mulford DA, Scheinberg DA, Jurcic JG (2005) The promise of targeted {alpha}-particle therapy. J Nucl Med 46(Suppl 1):199S–204S

    Google Scholar 

  91. Kim YS, Brechbiel MW (2012) An overview of targeted alpha therapy. Tumour Biol 33:573–590

    CAS  Google Scholar 

  92. Vaidyanathan G, Zalutsk MR (1996) Targeted therapy using alpha emitters. Phys Med Biol 41(10):1915–1931

    CAS  Google Scholar 

  93. Elgqvist J J (2011) Targeted alpha therapy: Part I. Curr Radiopharm 2(4):1–76

    Google Scholar 

  94. Morgenstern A, Bruchertseifer F, Apostolidis C (2012) Bismuth-213 and actinium-225—generator performance and evolving therapeutic applications of two generator-derived alpha-emitting radioisotopes. Curr Radiopharm 4:221–227

    Google Scholar 

  95. Miederer M, Scheinberg DA, McDevitt MR (2008) Realizing the potential of the actinium-225 radionuclide generator in targeted alpha particle therapy applications. Adv Drug Deliv Rev 60:1371–1382

    CAS  Google Scholar 

  96. 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

    CAS  Google Scholar 

  97. Ma D, McDevitt MR, Finn RD, Scheinberg DA (2001) Breakthrough of 225Ac and its radionuclide daughters from an 225Ac/213Bi generator: development of new methods, quantitative characterization, and implications for clinical use. Appl Radiat Isot 55:667–678

    CAS  Google Scholar 

  98. Schwartz J, Jaggi JS, O’Donoghue JA, Ruan S, McDevitt M, Larson SM, Scheinberg DA, Humm JL (2011) Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody. Phys Med Biol 56(3):721–733

    CAS  Google Scholar 

  99. Miederer M, McDevitt MR, Borchardt P, Bergman I, Kramer K, Cheung NK, Scheinberg DA (2004) Treatment of neuroblastoma meningeal carcinomatosis with intrathecal application of alpha-emitting atomicnanogenerators targeting disialo-ganglioside GD2. Clin Cancer Res 10(20):6985–6992

    CAS  Google Scholar 

  100. Ballangrud AM, Yang WH, Palm S, Enmon R, Borchardt PE, Pellegrini VA, McDevitt MR, Scheinberg DA, Sgouros G (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(13):4489–4497

    CAS  Google Scholar 

  101. Borchardt PE, Yuan RR, Miederer M, McDevitt, Scheinberg DA (2003) Targeted actinium-225 in vivo generators for therapy of ovarian cancer. Cancer Res 63(16):5084–5090

    CAS  Google Scholar 

  102. Miederer M, Scheinberg DA, McDevitt MR (2008) Realizing the potential of the actinium-225 radionuclide generator in targeted alpha particle therapy applications. Adv Drug Deliv Rev 60(12):1371–1382

    CAS  Google Scholar 

  103. Huclier-Markai S, Alliot C, Varmenot N, Cutler CS CS, Barbet J (2012) Alpha-emitters for immuno-therapy: a review of recent developments from chemistry to clinics. Curr Top Med Chem 12:2642–2654

    CAS  Google Scholar 

  104. Roscher M, Hormann I, Leib O, Marx S, Moreno J, Miltner E, Friesen C (2013) Targeted alpha-therapy using [Bi-213]anti-CD20 as novel treatment option for radio- and chemoresistant non-Hodgkin lymphoma cells. Oncotarget 4:218–230

    Google Scholar 

  105. Friesen C, Roscher M, Hormann I, Leib O, Marx S, Moreno J, Miltner E (2013) 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 49:2542–2554

    CAS  Google Scholar 

  106. Kluetz PG, Pierce W, Maher VE, Zhang H, Tang S, Song P, Liu Q, Haber MT, Leutzinger EE, Al-Hakim A, Chen W, Palmby T, Alebachew E, Sridhara R, Ibrahim A, Justice R, Pazdur R (2014) Radium (Ra 223) dichloride injection: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res 20(1):9–14

    CAS  Google Scholar 

  107. Shirley M, McCormack PL (2014) Radium-223 dichloride: a review of Its use in patients with castration-resistant prostate cancer with symptomatic bone metastases. Drugs 74(5):579–586

    CAS  Google Scholar 

  108. Hafeez S, Parker C (2013) Radium-223 for the treatment of prostate cancer. Expert Opin Investig Drugs 22(3):379–387

    CAS  Google Scholar 

  109. Chiu J-H, Landolt RR, Kessler WV (1978) Separation of rhodium-103 by solvent extraction. Anal Chem 50:670–671

    CAS  Google Scholar 

  110. Epperson CE, Landolt RR, Kessler WV (1976) Solvent–solvent extraction of rhodium-103m from ruthenium-103 employing a sulfate-carbon tetrachloride medium. Anal Chem 48(7):979–981

    CAS  Google Scholar 

  111. Skarnemark G, Ödegaard-Jensen A, Nilsson J, Bartos B, Kowalska E E, Bilewicz A, Bernhardt P (2009) Production of 103mRh for cancer therapy. J Radioanal Nucl Chem 280(2):371–373

    CAS  Google Scholar 

  112. Bartos B, Kowalska E, Bilewicz A, Skarnemark G (2009) 103Ru/103mRh generator. J Radioanal Nucl Chem 279(2):655–657

    CAS  Google Scholar 

  113. Boll R, Malkemus D, Mirzadeh S (2005) Production of actinium-225 for alpha particle mediated radioimmunotherapy. App Radiat Isot 62:667–679

    CAS  Google Scholar 

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Acknowledgments

Research at the Bhabha Atomic Research Centre (BARC) is part of the ongoing activities of the Department of Atomic Energy, India and is fully supported by government funding.

Conflict of interest

The authors have neither received any outside funding nor any grants from any external agencies in support of this study. None of the authors in this manuscript have any conflict of interest, financial or otherwise in the publication of this material.

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Authors and Affiliations

  1. Medical Radioisotope Program, Oak Ridge National Laboratory (ORNL), Bldg. 4501, MS 6229, 1 Bethel Valley Rd, PO Box 2008, Oak Ridge, TN, 37831-6229, USA

    F. F. Knapp Jr.

  2. Molecular Group of Companies, Kochi, 680001, Kerala, India

    M. R. A. Pillai

  3. Division of Physical and Chemical Sciences, Department of Nuclear Sciences and Applications, International Atomic Energy Agency (IAEA), Vienna International Centre, PO Box 100, 1400, Vienna, Austria

    J. A. Osso Jr.

  4. Isotope Production and Applications Division, Bhabha Atomic Research Centre (BARC), Trombay, Mumbai, 400 085, India

    Ashutosh Dash

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  1. F. F. Knapp Jr.
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  4. Ashutosh Dash
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Knapp, F.F., Pillai, M.R.A., Osso, J.A. et al. Re-emergence of the important role of radionuclide generators to provide diagnostic and therapeutic radionuclides to meet future research and clinical demands. J Radioanal Nucl Chem 302, 1053–1068 (2014). https://doi.org/10.1007/s10967-014-3642-8

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