Abstract
In addition to the key roles which research reactors and accelerators play in the direct availability of radioisotopes for therapy at dedicated production sites, a third common mode for availability is the on-demand in-house elution of daughter radioisotopes from radioisotope generator production systems. The parent specie for such generator systems are generally either reactor- or accelerator-produced. In this chapter, the concepts associated with the fabrication and use of radionuclide generators which provide therapeutic radioisotopes are described, and key generator systems of current or expected interest are described in detail.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abbasi IA, Zaidi JH, Arif M, et al. Measurement of fission neutron spectrum averaged cross sections of some threshold reactions on zirconium: production possibility of no-carrier-added 90Y in a nuclear reactor. Radiochim Acta. 2006;94:38.
Antczak C, Jaggi JS, Lefavre CV, Curico MJ, McDevitt MR, Scheinberg DA. Influence of the linker on the biodistribution and catabolism of actinium-225 self-immolative tumor-targeted isotope generators. Bioconjug Chem. 2006;17:1551–60.
Anwar M, Lathrop K, Rosskelly D, Harpen PV, Lathrop K, Rosselly D. Pertechnetate production from 99Mo by liquid-liquid extraction. J Nucl Med. 1968;9:298–9.
Asavatanabodee P, Sholter D, Davis P. Yttrium-90 radiochemical synovectomy in chronic knee synovitis: a one year retrospective review of 133 treatment interventions. J Rheumatol. 1997;24(4):639–42.
Atcher RW, Friedman AM, Hines JJ. An improved generator for the production of 212Pb and 212Bi from 224Ra. Int J Rad Appl Instrum A. 1988;39:283–6.
Bartos B, Kowaslka E, Bilewicz A, Skarnemark G. 103Ru/103mRh generator. J Lab Cmpds Radiopharm. 2007;50:S94.
Bartos B, Kowaslka E, Bilewicz A, Skarnemark G. 103Ru/103mRh generator. J Radioanal Nucl Chem. 2009;279:655–7.
Bateman H. Solution of a system of differential equations occurring in the theory of radioactive transformations. Proc Cambridge Philos Soc. 1910;15:423–7.
Beard SJ, Moore RL. Large-scale recovery and purification of fission products. In: Stevenson CE, Mason EA, Gresky AT, editors. Progress in nuclear energy (series III), process chemistry, vol. 4. London: Pergamon Press; 1969. p. 645.
Bilewicz A. Separation of 90Y from 90Sr on crystalline antimonic acid. Radiochim Acta. 1995;69:137–40.
Blower PJ, Kettle AG, O’doherty MJO, Coakley AJ, Knapp Jr FF. (99 m)Tc(V)DMSA quantitatively predicts (188)Re(V)DMSA distribution in patients with prostate cancer metastatic to bone. Eur J Nucl Med. 2000;27:1405–9.
Bodet-Milin C, Ferrer L, Pallardy A, Eugène T, et al. Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma. Front Oncol. 2013;3:177.
Boll RA, Mirzadeh S, Kennel SJ. Optimization of radiolabeling of immunoproteins with 213Bi. Radiochim Acta. 1997;79:145–9.
Boll RA, Malkemus D, Mirzadeh S. Production of actinium-225 for alpha particle mediated radioimmunotherapy. Appl Radiat Isot. 2005;62:667–79.
Braun T, Imura H, Suzuki N. Separation of 99mTc from parent 99Mo by solid-phase column extraction as a simple option for a new 99mTc generator concept. J Radioanal Nucl Chem Letters. 1987;119:315–25.
Bray LA. The recovery and purification of multi-kilocurie quantities of fission product strontium by cation exchange, Rep. HW-70998, Hanford Atomic Products Operation, Richland, 1961.
Bray LA, Wester DW. Method of preparation of yttirum-90 from strontium-90. US Patent # 5,512,256, 30 Apr 1996.
Bruland OS, Jostein D, Olsen DR, Larsen RH. Targeted high-LET therapy of bone metastases. Chapter 10. In: Stigbrand T, et al., editor. Targeted radionuclide tumor therapy. Springer Netherlands; 2008. p. 181–184. ISBN 978-1-4020-8695-3 (hard cover); DOI: 10.1007/978-1-4020-8696-0.
Buchmann I, Bunjes D, Kotzerke J, Martin H, Glatting G, Seitz U, Rattat D, Buck A, Döhner H, Reske SN. Myeloablative radioimmunotherapy with Re-188-anti-CD66-antibody for conditioning of high-risk leukemia patients prior to stem cell transplantation: biodistribution, biokinetics and immediate toxicities. Cancer Biother Radiopharm. 2002;17:151–63.
Bugai JE, Bickel EM, Azure MT, Friebe M, Lister-James J, Dean RT, Dinkelborg LM. Radiotherapeutic efficacy of a SSTR-targeting peptide (188Re-P2045) in a small cell lung cancer (SCLC) mouse model. J Nucl Med. 2002;43:123.
Bunjes D. 188Re-labeled anti-CD66 monoclonal antibody in stem cell transplantation for patients with high-risk acute myeloid leukemia. Leuk Lymphoma. 2002;43:2125–31.
Callahan AP, Rice DE, Knapp Jr FF. Rhenium-188 for therapeutic applications from an alumina-based tungsten-188/rhenium-188 generator. NucCompact. 1989;20:3–6.
Chakravarty R, Pandey U, Manolkar RB, et al. Development of an electrochemical 90Sr-90Y generator for separation of 90Y suitable for targeted therapy. Nucl Med Biol. 2008;35:245–53.
Chakravarty R, Dash A, Kothari K, et al. A novel 188W/188Re electrochemical generator with potential for medical applications. Radiochim Acta. 2009;97:309–17.
Chakravarty R, Dash A, Venkatesh M. A novel electrochemical technique for the production of clinical grade 99mTc using (n, gamma)99Mo. Nucl Med Biol. 2010a;37:21–8.
Chakravarty R, Dash A, Pillai MRA, Venkatesh M. Post-elution concentration of 188Re by an electrochemical method. Appl Radiat Isot. 2010b;68:2302–5.
Chakravarty R, Das T, Dash A, Venkatesh M. An electro-amalgamation approach to isolate no-carrier-added 177Lu from neutron irradiated Yb for biomedical applications. Nucl Med Biol. 2010c;37(7):811–20.
Chakravarty R, Dash A, Pillai MRA. Electrochemical separation is an attractive strategy for development of radionuclide generators for medical applications. Curr Radiopharm. 2012a;5:271–87.
Chakravarty R, Dash A, Pillai MRA. Availability of yttrium-90 from strontium-90: a nuclear medicine perspective. Cancer Biother Radiopharm. 2012b;27:621–41.
Chakravarty R, Dash A. Development of radionuclide generators for biomedical applications, Lambert Academic Publishing GmbH & Co. KG Heinrich-Böcking-Str. 6–8 66121, Saarbrücken, 2013.
Chang MY, Seideman J, Sofou S. Enhanced loading efficiency and retention of 225Ac in rigid liposomes for potential targeted therapy of micrometastases. Bioconjug Chem. 2008;19:1274–82.
Chapuy B, Hohloch K, Trümper L. Yttrium 90 ibritumomab tiuxetan (Zevalin): a new bullet in the fight against malignant lymphoma? Biotechnol J. 2007;2:1435–43.
Chattopadhyay S, Das SS, Das MK, Goomer NC. Recovery of 99mTc from Na2[99Mo]MoO4 solution obtained from reactor-produced (n, g) 99Mo using a tiny Dowex-1 column in tandem with a small alumina column. Appl Radiat Isot. 2008;66:1814–7.
Cheson BD. The role of radioimmunotherapy with yttrium-90 ibritumomab tiuxetan in the treatment of non-Hodgkin lymphoma. BioDrugs. 2005;19:309–22.
Cheung MC, Haynes AE, Stevens A, et al. Yttrium 90 ibritumomab tiuxetan in lymphoma. Leuk Lymphoma. 2006;47:967–77.
Chinol M, Franceschini R, Paganelli G, Pecorale A, Paiano A. Simple production of Yttrium-90 in a chemical form suitable to clinical grade radioconjugates radioactive isotopes in clinical medicine and research. In: Bergmann H, Kroiss A, Sinzinger H, editors. Advances in pharmacological science. Badgastein: Birkhäuser Basel; 1997. p. 327–32. DOI: 10.1007/978-3-0348-7772-5; Softcover ISBN 978-3-0348-7774-9
Chinol M, Hnatowich DJ. Generator-produced yttrium-90 for radioimmunotherapy. J Nucl Med. 1987;28:1465–70.
Chiu JH, Landolt RR, Kessler WV. Separation of rhodium-103 m from ruthenium-103 by solvent extraction. Anal Chem. 1978;50:670–1.
Christian JD, Pett DA, Kirkham RJ, Bennett RG. Advances in sublimation separation of technetium from low specific activity molybdenum-99. Ind Eng Chem Res. 2000;39(9):3157–68.
Chuang JT, Lo JG. Extraction chromatographic separation of carrier-free 90Y from 90Sr/90Y generator by crown ether coated silica gels. J Radioanal Nucl Chem. 1996;204:83–93.
Cwikla JB, Sankowski A, Seklecka N, et al. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010;21:787–94.
Dadachova E, Mirzadeh S, Lambrecht RM, Hetherington E, Knapp Jr FF. Separation of carrier-free holmium-166 from neutron-irradiated dysprosium targets. Anal Chem. 1995a;66:4272–7.
Dadachova E, Mirzadeh S, Lambrecht RM, Hetherington EL, Knapp Jr FF. Separation of carrier-free 166Ho from Dy2O3 targets by partition chromatography and electrophoresis. J Radioanal Nucl Chem Lett. 1995b;1999:115–23.
Dadachova E, Mirzadeh S, Smith SV, Knapp Jr FF, Hetherington EL. Radiolabeling antibodies with holmium-166. Appl Radiat Isot. 1997;48:477–81.
Dash A, Chakravarty R. Pivotal role of separation chemistry in the development of radionuclide generators to meet clinical demands. RSC Adv. 2014a;4:42779–803.
Dash A, Chakravarty R. Electrochemical separation: promises, opportunities, and challenges to develop next-generation radionuclide generators to meet clinical demands. Ind Eng Chem Res. 2014b;53:3766–77.
Dash A, Knapp FF (Russ) Jr. An overview of radioisotope separation technologies for development of 188W/188Re radionuclide generators providing 188Re to meet future research and clinical demands. RSC Adv. 2015;5:39012–36.
Dash A, Knapp FF (Russ) Jr, Pillai MRA. 99Mo/99mTc separation: an assessment of technology options. Nucl Med Biol. 2013;40(2):167–76.
Davies AJ. Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I131 tositumomab. Oncogene. 2007;26:3614–28.
Dietz ML, Horwitz EP. Applications of extraction chromatography in the development of radionuclide generator systems for nuclear medicine. Ind Eng Chem Res. 2000;39(9):3181–8.
Dillman RO. Radioimmunotherapy of B-cell lymphoma with radiolabelled anti-CD20 monoclonal antibodies. Clin Exp Me. 2006;6:1–12.
El-Amm J, Aragon-Ching JB. Radium-223 for the treatment of castration-resistant prostate cancer. Onco Targets Ther. 2015;8:1103–9.
Emmanouilides C. Review of Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy for B-cell follicular non-Hodgkin’s lymphoma. Cancer Manag Res. 2009;1:131–6.
Epperson CE, Landolt RR, Kessler WV. Solvent – solvent extraction of rhodium-103 m from ruthenium-103 employing a sulfate-carbon tetrachloride medium. Anal Chem. 1976;48:979–81.
Geerlings MW, Kaspersen FM, Apostolidis C, Van Der Hout R. The feasibility of 225Ac as a source of alpha-particles in radioimmunotherapy. Nucl Med Commun. 1993;14:121–5.
Gerse J, Kern J, Imre J, Zsinka L. Examination of a portable99Mo/99mTc isotope generator: SUBLITECH. J Radioanal Nucl Che. 1988;128(1):71–9.
Gisselbrecht C, Bethge W, Duarte RF, et al. Current status and future perspectives for yttrium-90(90)Y)-ibritumomab tiuxetan in stem cell transplantation for non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2007;40:1007.
Goffredo V, Paradiso A, Ranieri G, et al. Yttrium-90 (90Y) in the principal radionuclide therapies: an efficacy correlation between peptide receptor radionuclide therapy, radioimmunotherapy and transarterial radioembolization therapy. Ten years of experience (1999–2009). Crit Rev Oncol Hematol. 2011;80(3):393–410.
Guhlke S. Convenient concentration of 188Re perrhenate or 99mTc pertechnetate eluates from 188W/188Re or (n, \( g \)) produced 99Mo/99mTc generators to high specific volumes. J Label Compd Radiopharm. 1998;40:294.
Guhlke S, Beets AL, Oetjen K, et al. Simple new method for effective concentration of 188Re solutions from alumina-based 188W-188Re generator. J Nucl Med. 2000;41:1271–80.
Hagenbeek A. Radioimmunotherapy for NHL: experience of 90Y-ibritumomab tiuxetan in clinical practice. Leuk Lymphoma. 2003;44:S37–47.
Hassfjell S, Brechbiel MW. The development of the alpha-particle emitting radionuclides 212Bi and 213Bi, and their decay chain related radionuclides, for therapeutic applications. Chem Rev. 2001;101:2019–36.
Henriksen G, Hoff P, Alstad J, Larsen RH. 223Ra for endoradiotherapeutic applications prepared from an immobilized 227Ac/227Th source. Radiochim Acta. 2001;89:661–6.
Henriksen G, Schoultz BW, Michaelsen TE, et al. Sterically stabilized liposomes as a carrier for alpha-emitting radium and actinium radionuclides. Nucl Med Biol. 2004;31:441–9.
Hoeher M, Woerle J, Wohlfrom M, Hanke H, Voisard R, Osterhaus HH, Kochs M, Reske SN, Hombach V, Kotzerke J. Intracoronary β-irradiation with a liquid 188Re-filled balloon six-month results from a clinical safety and feasibility study. Circulation. 2000;101:2355–60.
Hong YD, Park KB, Jang BS, Choi SJ, Choi SM, Kim YM. Holmium-166-DTPA as a liquid source for endovascular brachytherapy. Nucl Med Biol. 2002;29:833–9.
Horwitz EP, Dietz ML, Fisher DE. SREX: a new process for the extraction and recovery of strontium from acidic nuclear waste streams. Solv Extr Ion Exch. 1991;9:1.
Hsieh BT, Ting G, Hsieh HT, Shen LH. Preparation of carrier-free yttrium-90 for medical applications by solvent extraction chromatography. Appl Radiat Isot. 1993;44:1473–80.
Iznaga-Escobar N. Direct radiolabeling of monoclonal antibodies with rhenium-188 for radioimmunotherapy of solid tumors–a review of radiolabeling characteristics, quality control and in vitro stability studies. Appl Radiat Isot. 2001;54:399–406.
Jäckel B, Cripps R, Güntay S, Bruchertseifer H. Development of semi-automated system for preparation of (188)Re aqueous solutions of high and reproducible activity concentrations. Appl Radiat Isot. 2005;63:299–304.
Jassin LE. Radiochemical separation advancements using extraction chromatography: a review of recent Eichrom users’ group workshop presentations with a focus on matrix interferences. J Radioanal Nucl Chem. 2005;163:93–6.
Jennewein M, Qaim SM, Kulkarni PV, et al. A no-carrier-added 72Se/72As radionuclide generator based on solid phase extraction. Radiochim Acta. 2005;93:579–83.
Jeong JM, Chung JK. Therapy with 188Re-labeled radiopharmaceuticals: an overview of promising results from initial clinical trials. Cancer Biother Radiopharm. 2003;18:707–17.
Jeong JM, Kim YJ, Lee YS, et al. Lipiodol solution of a lipophilic agent, 188Re-TDD, for the treatment of liver cancer. Nucl Med Biol. 2001;28:197–204.
Jeong JM, Knapp Jr FF. Use of the Oak Ridge National Laboratory tungsten-188/rhenium-188 generator for preparation of the rhenium-188 HDD/lipiodol complex for trans-arterial liver cancer therapy. Semin Nucl Med. 2008;38(2):S19–29.
Jurcic JG, Larson SM, Sgouros G, et al. Targeted alpha particle immunotherapy for myeloid leukemia. Blood. 2002;100:1233–9.
Jurcic JG, Rosenblat TL. Targeted alpha-particle immunotherapy for acute myeloid leukemia. Am Soc Clin Oncol Educ Book. 2014; e126-31. doi: 10.14694/EdBook_AM.2014.34.e126
Kamadhenu Electrochemical 90Sr/90Y generator, Model KA 01 Operating Manual. Isotope Technologies Dresden, 2010.
Kamioki H, Mirzadeh S, Lambrecht RM, et al. 188W/ 188Re generator for biomedical applications. Radiochim Acta. 1994;65:39–46.
Kampen WU, Voth M, Pinkert J, Krause A. Therapeutic status of radiosynoviorthesis of the knee with yttrium [90Y] colloid in rheumatoid arthritis and related indications. Rheumatology (Oxford). 2007;46:16–24.
Kan RW, Tsang SH, Poon RT, Cheung TT. Update on yttrium-90-based radio-embolization for treatment of hepatocellular carcinoma. ANZ J Surg. 2012;82:505–9.
Ketring AR, Ehrhardt GJ, Embree MF, Bailey KD, Tyler TT, Gawenis JA, Jurisson SS, Englebrecht HP, Smith CJ, Cutler CS. Production and supply of high specific activity radioisotopes for radiotherapy applications. Revista Med Nucl Alasbimn J. 2002;5:1.
Knapp FF (Russ) Jr, Beets AL, Mirzadeh S, Guhlke S. Concentration of perrhenate and pertechnetate solutions. U.S. Patent No. 5,729,821. 1998.
Knapp FF (Russ) Jr, Beets AL, Mirzadeh S, Guhlke S. Use of a new tandem cation/anion exchange system with clinical-scale generator provides high specific volume solution of technicium-99m and rhenium-188. In: Proceedings, international trends in radiopharmaceuticals for diagnosis and therapy. Lisbon, Portugal, Mar 30–Apr 1998.
Knapp FF Jr, Butler TA, editor. Radionuclide generators: new systems for nuclear medicine applications. 241 ACS Symposium Series, American Chemical Society, United States, 1984.
Knapp Jr FF, Mirzaeh S. The continuing important role of radionuclide generator systems for nuclear medicine. Eur J Nucl Med. 1994;21:1151–65.
Knapp Jr FF, Lisic EJ, Mirzadeh S, et al. A new clinical prototype W-188/Re-188 generator to provide high levels of carrier-free Rhenium-188 for radioimmunotherapy. Eur J Nucl Med. 1991;18:538.
Knapp FF, Lisic EC, Mirzadeh S, Callahan AP. Tungsten-188/carrier-free rhenium-188 Perrhenic acid generator system. U.S. Patent No. 5,186,913; 1993.
Knapp Jr FF, Callahan AP, Beets AL, Mirzadeh S. Processing of reactor-produced 188W for fabrication of clinical scale alumina based 188W/188Re Generators. Appl Radiat Isot. 1994;45:1123–8.
Knapp Jr FF, Beets AL, Guhlke S, et al. 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. 1997;17:1783–95.
Knapp Jr FF, Beets AL, Mirzadeh S, Guhlke S. Use of a new tandem cation/anion exchange system with clinical—scale generators provides high specific volume solutions of technetium-99m and rhenium-188, IAEA-ECDOC-1029. Vienna: IAEA; 1998. p. 419–25.
Knapp Jr FF, Pillai MRA, Osso Jr JA, Dash A. 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. 2014;302:1053–68.
Kotzerke J, Hanke J, Hocher M. Endovascular brachytherapy for the prevention of restenosis after angioplasty. Eur J Nucl Med. 2000;27:223–36.
Kropp J, Reynen K, Koeckeritz U, Wunderlich G, Schmeisser A, Strasse RH, Knapp Jr FF. Prevention of in-stent stenosis with liquid filled 188Re balloon: the Dresden in-stent restenosis trial (DIRRT). World J Nucl Med. 2002;1:S13.
Lambert B, de Klerk JM. Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy. Nucl Med Commun. 2006;27:223–9.
Lange G, Herrmann G, Strassmann F. Preparation of strontium-90 free yttrium-90 by electrolysis. J Inorg Nucl Chem. 1957;4:146.
Larsen RH, Saxtorph H, Skydsgaard M, et al. Radiotoxicity of the alpha-emitting bone-seeker 223Ra injected intravenously into mice: histology, clinical chemistry and hematology. Vivo. 2006;20(3):325–33.
Larsen SH, Borrebaek J, Dahle J, Melhus KB, Krogh MH, Valan MH, Bruland OS. Preparation of Th-227-labeled radioimmunoconjugates, assessment of serum stability and antigen binding ability. Cancer Biother Radiopharm. 2007;22:431–7.
Lau WY, Lai EC, Leung TW. Current role of selective internal irradiation with yttrium-90 microspheres in the management of hepatocellular carcinoma: a systematic review. Int J Radiat Oncol Biol Phys. 2011;81(2):460–7.
Lee JS, Lee J-S, Park U-J, Son K-J, Han H-S. One column operation for (90)Sr/(90)Y separation by using a functionalized-silica. Appl Radiat Isot. 2009;67:1332–5.
Lewis RE. Production of 70-day tungsten-188 and development of a 17 hour rhenium-188 radioisotope generator. J Nucl Med. 1966;7:804–5.
Lien LME, Tvedt B, Heinrich D. Treatment of castration-resistant prostate cancer and bone metastases with radium-223 dichloride. Int J Urol Nurs. 2015;9(1):3–13.
Lisic EC, Callahan AP, Mirzadeh S, Knapp Jr FF. The tandem tungsten-188/rhenium-188 Perrhenate/Perrhenic acid generator system. Radioact Radiochem. 1992;3:42–5.
Lumetta GJ, Wester DW, Morrey JR, Wagner MJ. Preliminary evaluation of chromatographic techniques for the separation of radionuclides from high level radioactive waste. Solv Extr Ion Exch. 1993;11:663.
Macháň V, Vilček S, Kalinčák M. Technetium-99m sublimation from molybdenum trioxide eutectic mixtures. J Inorg Nucl Chem. 1981;43:3063–6.
Makkar R, Whiting JA, Hidehiko H, Fishbien MC, Knapp Jr FF, Litvack F, Eigler NL. Effects of beta(−)-emitting (188)Re balloon in stented porcine coronary arteries: an angiographic, intravascular ultrasound, and histomorphometric study. Circulation. 2000;102:3117–23.
Marincek N, Jörg AC, Brunner P. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study. J Transl Med. 2013;15:11–7.
Mausner LF, Kolsky KL, Joshi V, Srivastava SC. Radionuclide development at BNL for nuclear medicine therapy. Appl Radiat Isot. 1998;49(4):285–94.
McDevitt MR, Finn RD, Sgouros G, Ma D, Scheinberg DA. An 225Ac/213Bi generator system for therapeutic clinical applications: construction and operation. Appl Radiat Isot. 1999a;50:895–904.
McDevitt MR, Finn RD, Sgorous G, Ma D, Scheinberg DA. Preparation of alpha-emitting 213Bi-labeled antibody constructs for clinical use. J Nucl Med. 1999b;40:1722–7.
McDevitt MR, Ma D, Lai LT, Simon J, Borchardt P, Frank RK, Wu K, Pellegrini V, Curcio MJ, Miederer M, Bander NH, Scheinberg DA. Tumor therapy with targeted atomic nanogenerators. Science. 2001;294:1537–40.
Micallef IN. Ongoing trials with yttrium 90-labeled ibritumomab tiuxetan in patients with non-Hodgkin’s lymphoma. Clin Lymphoma. 2004;5:S27–32.
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;60:1371–82.
Mikheev NS, Popovich VS, Rumer IA, Volkova NC. Rhenium-188 generator. Isotopenpraxis. 1972;8:248–51.
Mirzadeh S, Knapp Jr FF. Biomedical radioisotope generator systems. J Radioanal Nucl Chem. 1996;203:471–88.
Mirzadeh S, Knapp Jr FF, Lambrecht RM. Burn-up cross section of 188W. Radiochim Acta. 1997;77:99–110.
Mirzadeh S, Lambrecht RM. Excitation function for the 209Bi(7Li, 5n)211Rn nuclear reaction. Int J Appl Radiat Isot. 1980;31:351–5.
Miszczyk L, Wozniak G, Jochymek B, Spindel J, Wygoda Z. Effectiveness evaluation of knee joint 90Y radiosynovectomy. Przegl Lek. 2007;64:450–3.
Mirzadeh S. Generator-produced alpha-emitters. Appl Radiat Isot. 1998;49:345–9.
Montaña RL, González IH, Ramirez AA, et al. Yttrium-90 – current status, expected availability and applications of a high beta energy emitter. Curr Radiopha. 2012;5(3):253–6.
Mukherji D, Dika IE, Temraz S, Haidar M, Shamseddine A. Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer – role of radium-223. Ther Clin Risk Mana. 2014;10:373–80.
Murray A, Simms MS, Scholfield DP, Vincent RM, Denton G, Bishop MC, Price MR, Perkins AC. Production and characterization of 188Re-C595 antibody for radioimmunotherapy of transitional cell bladder cancer. J Nucl Med. 2001;42:726–32.
Mushtaq A, Bukhari TH, Khan IU. Extraction of medically interesting 188Re-perrhenate in methyl ethyl ketone for concentration purposes. Radiochimica Acta. 2007;95:535–53.
Nilsson S, Franzen L, Parker C, Tyrell C, Blom R, Tennevall J, Lenneras B, Petersson U, Johannessen DC, Sokail M, Pigott K, Yachnin J, Garkavij M, Strang P, Harmenberg J, Bolstad B, Bruland OS. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007;8(7):587–94.
Nowak B, Meyer JMA, Goergen T, Fluehs D, Block S, Guenther RW, Howecker H, Buell U. Dosimetry of a 188rhenium-labeled self-expanding stent for endovascular brachytherapy in peripheral arteries. Cardiovasc Radiat Med. 2001;2:246–63.
Ofluoglu S, Schwameis E, Zehetgruber H, Havlik E, Wanivenhaus A, Schweeger I, Weiss K, Sinzinger H, Pirich C. Radiation synovectomy with (166)Ho-ferric hydroxide: a first experience. J Nucl Med. 2002;43:1489–94.
Orth RJ, Kurath DE. Review and assessment of technologies for the separation of strontium from alkaline and acidic media, Rep. PNL-9053, Pacific Northwest National Laboratory, Richland, 1994.
Osso J, Knapp Jr FF. Invited, Chapter 21: Principles and operation of radionuclide generators. In: Sampson’s textbook on radiopharmacy. 4th ed. London: Pharmaceutical Press; 2011. p. 339–64. ISBN 978 0 85369 789 3.
Pandey U, Dhami PS, Jagesia P, et al. A novel extraction paper chromatography (EPC) technique for the radionuclidic purity evaluation of 90Y for clinical use. Anal Chem. 2008;80:801.
Park SW, Hong MK, Moon DH, Oh SJ, Lee CW, Kim JJ, Park SJ. Treatment of diffuse in-stent restenosis with rotational atherectomy followed by radiation therapy with a rhenium-188-mercaptoacetyltriglycine-filled balloon. J Am Coll Cardiol. 2001;38:631–7.
Pfost B, Seidl C, Autenrieth M, et al. Intravesical alpha-radioimmunotherapy with 213Bi-anti-EGFR-mAb defeats human bladder carcinoma in xenografted nude mice. J Nucl Med. 2009;50:1700–8.
Pillai MR, Dash A, Knapp Jr FF. Rhenium-188: availability from the 188W/188Re generator and status of current applications. Curr Radiopharm. 2012;5:228–43.
Production of long lived parent radionuclides for generators: 68Ge, 82Sr, 90Sr and 188W (2010) IAEA Radioisotopes and Radiopharmaceuticals Series No. 2. Vienna: IAEA.
Rajendran JG, Eary JF, Bensinger W, Durack LD, Vernon C, Fritzberg A. High-dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation. J Nucl Med. 2002;43:1383–90.
Ramanujam A, Dhami PS, Chitnis RR, et al. Separation of strontium-90 from PUREX high level waste and development of 90Sr/90Y generator. BARC report 2000/E/009, BARC India, 2000.
Renzulli JF, Collins J, Mega A. Radium-223 dichloride: illustrating the benefits of a multidisciplinary approach for patients with metastatic castration-resistant prostate cancer. J Multidiscip Health. 2015;8:279–86.
Reske SN, Bunjes D, Buchmann I, Seitz U, Glatting G, Neumaier B, Kotzerke J, Buck A, Martin H, Döhner H, Bergmann L. Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation. Eur J Nucl Med. 2001;28:807–15.
Roesch F, Knapp FF Jr. Chapter 4: Radionuclide generators. In: Vertes A, Klencsar NS, Roesch F, editors. Handbook of nuclear chemistry. Vol 4, 2nd ed. Dordrecht: Kluwer Academic Publishers; 2011. p. 1935–76. ISBN 978-1-4419-0720-2.
Rutherford E, Soddy F. The cause and nature of radioactivity. Philos Mag. 1902;4:370–96; Part II 4:569–85.
Sarkar SK, Venkatesh M, Ramamoorthy N. Evaluation of two methods for concentrating perrhenate (188Re) eluates obtained from 188 W-188 Re generator. Appl Radiat Isot. 2009;67:234–9.
Sato KT. Yttrium-90 radioembolization for the treatment of primary and metastatic liver tumors. Semin Roentgenol. 2011;46:159–65.
Savelli G, Giubbini R. Yttrium-90 DOTATOC therapy in GEP-NET and other SST2 expressing tumors: a selected review. Ann Nucl Med. 2011;25:75–85.
Savio E, Gaudiano J, Robles AM, Balter H, Paolino A, Lo’pez A, Hermida JC, De Marco E, Martinez G, Osinaga E, Knapp Jr FF. Re-HEDP: pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose. BMC Nucl Med. 2001;1:2.
Scheinberg DA, McDevitt MR. Actinium-225 in targeted alpha-particle therapeutic applications. Curr Radiopharm. 2011;4:306–20.
Schuelen H, Eigler N, Whiting JS, Haubner R, Hausleiter J, Dirschinger J, Kastrati A, Schwaiger M, Schömig A. Usefulness of intracoronary brachytherapy for in-stent restenosis with a 188Re liquid-filled balloon. Am J Cardiol. 2001;87:463–6.
Sgouros G, Ballangrud AM, Jurcic JG, et al. Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia. J Nucl Med. 1999;40:1935–46.
Skarnemark G, Odegaard-Jense A, Nilsson J, Bartos B, Kowalska E, Bilewicz A, Bernhardt P. Production of 103mRh for cancer therapy. J Radioanalyt Nucl Chem. 2009;280:371–3.
Skuridin VS, Chibisov EV. Development of a small-size extractor for separation of the 99Mo/99mTc couple. Radiochemistry. 2010;52(1):90–4.
Smith SV, Di Bartolo N, Mirzadeh S, Lambrecht RM, Knapp Jr FF, Hetherington EL. [166Dy]dysprosium/[166Ho]holmium in vivo generator. Appl Radiat Isot. 1995;46:759–64.
Soderquist CZ, McNamara BK, Fisher DR. Production of high-purity radium-223 from legacy actinium-beryllium neutron sources. Curr Radiopharm. 2012;5:244–52.
Sofou S, Kappel BJ, McDevitt MR, Scheinberg DA, Sgorous G. Enhanced retention of the alpha-particle-emitting daughters of Actinium-225 by liposome carriers. Bioconjug Chem. 2007;18:2061–7.
Sundram FX, Yu S, Somanesan S, Jeong JM, Bernal P, Osorio M, Esguerra R, Chau TCM, Long HD, Hoa NV, Huy NDS, Onkhuudai P, Lamjav T, Zanzonica P, Divgi C, Padhy AK, Martindale A, Saw MM, Rolland Y, Knapp Jr FF. Phase I study of transarterial rhenium-188 HDD lipiodol in treatment of inoperable primary hepatocellular carcinoma – a multicentre evaluation. World J Nucl Med. 2002;1:5–11.
Szucs Z, Van Rooyen J, Zeevaart JR. A possible in vivo generator 103Pd/103mRh – recoil considerations. Appl Radiat Isot. 2008;66:1346–9.
Taylor WJ, Corkill MM, Rajapaske CN. A retrospective review of yttrium-90 synovectomy in the treatment of knee arthritis. Br J Rheumatol. 1997;36:1100–5.
Teiluf K, Seidl C, Blechert B, et al. α-Radioimmunotherapy with 213Bi-anti-CD38 immunoconjugates is effective in a mouse model of human multiple myeloma. Oncotarget. 2015;6(7):4692–703.
Teunissen JJ, Kwekkeboom DJ, Krenning EP. Staging and treatment of differentiated thyroid carcinoma with radiolabeled somatostatin analogs. Trends Endocrinol Metab. 2006;17:19–25.
Therapeutic Radionuclide Generators: 90Sr/90Y and 188W/188Re generators. IAEA Technical Report Series No. 470. Vienna: IAEA; 2009.
US Food and Drug Administration. Radium Ra 223 dichloride. Updated May 15 2013. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm352393.htm?source=govdelivery. Accessed 15 June 2014.
Vachtel VM, Vinel GV, Vylov T, Gromova II, Novgorodov AF, Norseev YV, Chumin VG, Khalkin VA. Gas-thermochromatographic method for astatine separation. Relative yield of astatine isotopes from uranium. Radiokhimiya. 1976;18:886.
Vinjamuri S, Gilbert TM, Banks M. Peptide receptor radionuclide therapy with 90Y-DOTATATE/ 90Y-DOTATOC in patients with progressive metastatic neuroendocrine tumours: assessment of response, survival and toxicity. Br J Cancer. 2013;108:1440–8.
Visser J, Brinkman GA, Bakker CNM. Production of astatine and radon isotopes by photospallation of 232Th and 238U. Int J Appl Radiat Isot. 1979;30:745–8.
Vuong W, Sartor O, Pal SK. Radium-223 in metastatic castration resistant prostate cancer. Asian J Androl. 2014;16:348–53.
Walker LA, Radioactive yttrium-90. A review of its properties, biological behaviour and clinical uses. Acta Radiol Ther Phys Biol. 1964;2:302–14.
Weigert O, Illidge T, Hiddemann W, Dreyling M. Recommendations for the use of yttrium-90 ibritumomab tiuxetan in malignant lymphoma. Cancer. 2006;107:686–95.
Weinberger J, Giedd KN, Simon AD, Marboe C, Knapp FF, Trichter F, Amols H. Radioactive beta-emitting solution-filled balloon treatment prevents porcine coronary restenosis. Cardiovasc Radiat Med. 1999a;1:252–6.
Weinberger J, Knapp Jr FF. Use of liquid-filled balloons for coronary irradiation. In: Waksman R, editor. Vascular brachytherapy. 2nd ed. Armonk: Futura Publishing; 1999b. p. 521–35. ISBN 0-87993-4131.
Wester DW, Steele RT, Rinehart DE, et al. Large-scale purification of 90Sr from nuclear waste materials for production of 90Y, a therapeutic medical radioisotope. Appl Radiat Iso. 2003;59:35–41.
Wick RR, Nekolla EA, Gaubitz M, Schulte TL. Increased risk of myeloid leukaemia in patients with ankylosing spondylitis following treatment with radium-224. Rheumatology (Oxford). 2008;47:855–9.
Winfield J, Gumpel JM. An evaluation of repeat intra-articular injections of yttrium-90 colloids in persistent synovitis of the knee. Ann Rheum Dis. 1979;38:145–7.
Wohlgemuth WA, Leissner G, Wengenmair H, Bohndorf K, Kirchhof K. Endovascular brachytherapy in the femoropopliteal segment using 192Ir and 188Re. Cardiovasc Intervent Radiol. 2008;31(4):698–708.
Wu C, Brechbiel MW, Gansow OA. An improved generator for the production of 213Bi from 225Ac. Radiochim Acta. 1997;79:141–4.
Wunderlich G, Hartmann H, Andreeff M, Kotzerke J. A semi-automated system for concentration of rhenium-188 for radiopharmaceutical applications. Appl Radiat Isot. 2008;66:1876–80.
Zalutsky MR, Pozzi OR. Radioimmunotherapy with alpha-particle emitting radionuclides. Q J Nucl Med Mol Imaging. 2004;48:289–96.
Zinzani PL, d'Amore F, Bombardieri E. Consensus conference: implementing treatment recommendations on yttrium-90 immunotherapy in clinical practice – report of a European workshop. Eur J Cancer. 2008;44:366–73.
Zsinka L. 99mTc sublimation generators. Radiochim Acta. 1987;41:91–6.
Zykov MP, Romanovskii VN, Wester DW, et al. Use of extraction generator for preparing a 99mTc radiopharmaceutical. Radiochemistry. 2001;43:297–300.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer India
About this chapter
Cite this chapter
Knapp, F.F.(., Dash, A. (2016). Radionuclide Generator Systems Represent Convenient Production Systems to Provide Therapeutic Radionuclides. In: Radiopharmaceuticals for Therapy . Springer, New Delhi. https://doi.org/10.1007/978-81-322-2607-9_7
Download citation
DOI: https://doi.org/10.1007/978-81-322-2607-9_7
Published:
Publisher Name: Springer, New Delhi
Print ISBN: 978-81-322-2606-2
Online ISBN: 978-81-322-2607-9
eBook Packages: MedicineMedicine (R0)