Abstract
In this review, the continuing importance and status of development of radionuclide generator systems for nuclear medicine are discussed. Radioisotope costs and availability are two important factors, and both nuclear reactors and accelerator facilities are required for production of the parent radioisotopes. Radionuclide generator research is currently focused on the development of generators which provide radioisotopes for positron emission tomography (PET) applications and daughter radioisotopes for various therapeutic applications which decay primarily by particle emission. Generator research continues to be influenced by developments and requirements of complementary technologies, such as the increasing availability of PET. In addition, the availability of a wide spectrum of tumor-specific antibodies, fragments, and peptides for radio-immunodiagnosis and radioimmunotherapy has stimulated the need for generator-derived radioisotopes. The advantages of treatment of arthritis of the synovial joints with radioactive particles (radiation synovectomy) may be expected to be of increasing importance as the elderly population increases, and many of these agents are prepared using generator-derived radioisotopes such as yttrium-90 and rhenium-188. Therapeutic use of the “in vivo generator” is a new approach, where the less radio-toxic parent radioisotope is used to prepare tissue-speciic therapeutic agents. Following in vivo site localization, decay of the parent provides the daughter for therapy at the target site. The principal foundation of most diagnostic agents will continue to require technetium-99m from the molybdenum-99/technetium-99m (“Moly”) generator. With the limited availability of nuclear reactors and facilities necessary for production and processing of fission 99mTc and the significant issues and problems associated with radioactive waste processing, however, the possibility of utilizing lower specific activity 99Mo produced from neutron activation of enriched 98Mo may become practical in the future.
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References
Brucer M. Medical radioisotope cows. Isotopes Radiat Tech 1965;3:1–12.
Stang L. Radionuclide generators: past, present and future. Brookhaven National Laboratory Monograph, BNL 50186, T-541. New York, Brookhaven National Laboratory, 1969.
Lebowitz E, Richards P. Radionuclide generators. Semin Nucl Med 1974; 4:257–268.
Hnatowich DJ. A review of radiopharmaceutical development of short-lived generator-produced radionuclides other than 99mTc. Int J Appl Radiat Isotop 1977; 28:169–181.
Yano Y. Radionuclide generators: current and future applications in nuclear medicine. In: Subramanian G, Rhodes BA, Cooper JF, Sood VJ, eds. Radiopharmaceuticals. New York: Society of Nuclear Medicine; 1978:236–245.
Finn RD, Molinski VJ, Hupf HB, Kramer H. Radionuclide generators for biomedical applications. In: Nuclear science series, nuclear medicine. United States Department of Energy, NAS-NS-3202 (DE83016360), 1983.
Knapp FF Jr, Butler TA, eds. Radionuclide generators: new systems for nuclear medicine applications. American Chemical Society Advances in Chemistry Series No. 241. Washington, D.C. American Chemical Society (ISBN 0–8412–0822–0), 1984.
Lambrecht RM. Radionuclide generators. Radiochim Acta 1983; 34:9–24.
Guillaume M, Brihaye C. Generators of ultra-short lived radionuclides for routine clinical applications. Radiochim Acta 1987; 41:119–130.
Mani RS. Reactor production of radionuclides for generators. Radiochim Acta 1987;41:103–110.
Lambrecht RM, Sajjad M. Accelerator-derived radionuclide generators. Radiochim Acta 1988; 43:171–179.
Knapp FF, Callahan AP, Mirzadeh S, Brihaye C, Guillaume M. The development of radionuclide generators. In: Schubiger PA, Westera G, eds. Progress in radiopharmacy. Dordrecht: Kluwer Academic, 1992:67–88.
Knapp FF Jr, Brihaye C, Callahan AP. Radionuclide generator systems for nuclear medicine applications. In: Wagner HN, Szabo Z, eds. Principles of nuclear medicine, 2nd edn. New York: W.B. Saunders, in press.
Richards P. Technetium-99m: the early days. In: Nicolini M, Bandoli G, Mazzi U, eds. Technetium and rhenium in chemistry and nuclear medicine 3. New York: Cortina Publishers-International Raven Press; 1989:5–9.
Eckelman WC, Coursey BM, eds. Technetium-99m: generators, chemistry and preparation of radiopharmaceuticals. Int J Appl Radiat Isotop 1982; 33:793–806.
Holland ME, Deutsch E, Heineman WR. Studies on commercially available 99Mo/99mTc radionuclide generators. I. Comparison of five analytical procedures for determination of total technetium in generator eluants. Int J Appl Radiat Isotop 1986; 37:165–171.
Holland ME, Deutsch E, Heineman WR. Studies on commercially available 99Mo/99mTc radionuclide generators. II. Operating characteristics and behavior of 99Mo/99mTc generators. Int J Appl Radiat Isotop 1986; 37:173–180.
Boyd RE. Technetium generators: status and prospects. In: Seminar on radionuclide generator technology. IAEA-SR-131/11, 1986.
Boyd RE. Molybdenum-99/technetium-99m generator. Radiochim Acta 1982; 30:123–145.
Evans JV, Moore PW, Shying ME, Sodeau JM. A new generator for 99mTc. In: Raynuad C, ed. Proceedings of the 3rd world congress of nuclear medicine and biology, vol II. 29 August–2 September, Paris, France. New York: Pergamon Press; 1982:1592–1595.
Lisic E, Mirzadeh S, Callahan AP, Knapp IF Jr. A new tandem generator/ion exchange system providing carrier-free 188Re/perrhenic acid for antibody labeling [abstract]. J Nucl Med 1991; 32:945
Knapp IF Jr, Lisic EC, Mirzadeh S, Callahan AP. Tungsten-188/carrier-free 188Re perrhenic acid generator system. United States Patent No. 5,186,913; Issued 17 February, 1993.
Knapp FF Jr, Lisic EC, Mirzadeh S, Callahan AP. Tungsten-188/carrier-free 188Re perrhenic acid generator system. United States Patent No. 5,275,802; Issued 4 January, 1994.
Kamioki H, Mirzadeh S, Lambrecht RM, Knapp FF Jr, Dadachova E. 188W/188Re generator for biomedical applications. Radiochim Acta. 1994; (in press).
Spooren PFMJ, Rasker JJ, Arens RPJH. Synovectomy of the knee with 90Y. Eur J Nucl Med 1985; 10:441–445.
Deutsch E, Brodack JW, Deutsch KF. Radiation synovectomy revisted. Eur J Nucl Med 1993; 20:1113–1127.
Hoefnagel CA. Radionuclide therapy revisited. Eur J Nucl Med 1991; 18:408–431.
Volkert WA, Goeckeler WF, Ehrhardt GJ, Ketring AR. Therapeutic radionuclides: production and decay property considerations. J Nucl Med 1991; 32:174–185.
Wike JS, Guyer CE, Ramey DW, Phillips H. Chemistry for commercial sale production of 90Y for medical research. Int J Appl Radiat Isotop 1990; 41:861–865.
Anderson-Berg WT, Squire RA, Strand M. Specific radio-immunotherapy using 90Y-labeled monoclonal antibody in erythroleukemic mice. Cancer Res 1987; 47:1905–1912.
Sharkey RM, Kaltovich FA, Shih LB, Fand I, Govelitz G, Goldenberg DM. Radioimmunotherapy of human colonic cancer xenografts with 90Y labeled monoclonal antibodies to carcinoembryonic antigen. Cancer Res 1988; 48:3270–3275.
Order SE, Klein JL, Leichner PK, Frinke J, Lollo C, Carlo J. Yttrium-90 antiferritin. A new therapeutic radiolabeled antibody. Int J Radiat Oncol Biol Phys 1986; 12:227–281.
Chinol M, Hnatowich DJ. Generator-produced 90Y for radioimmunotherapy. J Nucl Med 1987; 28:1465–1470.
Hayes RL, Rafter JJ. Rhenium-188 as a possible diagnostic agent. In: Research report. Medical Division, Oak Ridge Associated Universities. ORAU 1965; 101:74–77.
Hayes RL, Rafter JJ. Rhenium-188 as a possible diagnostic agent [abstract]. J Nucl Med 1966; 7:797.
Lewis RE, Eldridge JS. Production of 70-day tungsten-188 and development of the 17 hour 188Re radioisotope generator [abstract]. J Nucl Med 1966; 7:804–805.
Callahan AP, Rice DE, Knapp FF, Jr. Availability of 188Re form a tungsten-188/188Re generator system for therapeutic applications [abstract]. J Nucl Med 1987; 28:657.
Callahan AP, Rice DE, Knapp FF Jr. Rhenium-188 for therapeutic applications from an alumina based tungsten-188/188Re radionuclide generator. NucCompact-Eur/Am Commun Nucl Med 1989; 20:3–6.
Callahan AP, Rice D, McPherson DW, Knapp FF Jr. The use of alumina SepPakSR as a simple method for the removal and determination of tungsten-188 breakthrough from tungsten 188/188Re generators. Int J Appl Radiat Isotop 1992; 43:801–804.
Ehrhardt G, Ketring AP, Turpin TA, Razavi MS, Vanderheyden J-L, Fritzberg AR. An improved tungsten-188/188Re generator for radiotherapeutic applications. J Nucl Med 1987; 28:656–657.
Ehrhardt G, Ketring AP, Turpin TA, Razavi MS, Vanderheyden J-L, Fu S-M, Fritzberg AR. A convenient tungsten188/188Re generator for therapeutic applications using low specific activity tungsten-188. In: Nicolini M, Bandoli G, eds. Technetium and rhenium in chemistry and nuclear medicine 3. New York: Corina International-Raven Press; 1990:631–634.
Kodina G, Tulskaya T, Gureev E, Brodskaya G, Gapurova O, Drosdovsky B. Production and investigation of 188Re generator. In: Nicolini M, Bandoli G, eds. Technetium and rhenium in chemistry and nuclear medicine 3. New York: Corina International-Raven Press; 1990: 635–641.
Knapp FF Jr, Lisic EC, Mirzadeh S, Callahan AP, Rice DE. A new clinical prototype tungsten-188/188Re generator to provide high levels of carrier-free 188Re for radioimmunotherapy (RAIT) [abstract]. Eur J Nucl Med 1991; 18:650.
Griffiths G, Knapp FF Jr, Callahan AP, Chang Z, Jones AL, Ostella F, Hansen HJ, Goldenberg DM. The use of carrier-free Re-188 from an in-house W-188/Re-188 generator for preparation of Re-188-labeled monoclonal antibodies [abstract]. J Nucl Med 1991; 32: 1098.
Griffiths GL, Knapp FF Jr, Callahan AP, Chang C-H, Hansen HJ, Goldenberg DM. Direct radiolabeling of monoclonal antibodies with generator-produced 188Re for radioimmunotherapy. Cancer Res 1991; 51:4592–4602.
Griffiths GL, Knapp FF Jr, Callahan AP, Ostella F, Hansen HJ, Goldenberg DM. The generation of 188Re-labeled antibodies by direct labeling methods. Seventh International Symposium on Radiopharmacology, Boston, Mass., 3–6 June, 1991.
Griffiths GL, Goldenberg DM, Diril H, Hansen HJ. Technetium-99m, rhenium-186 and 188Re direct-labeled antibodies. Cancer 1994; 73:761–768.
Griffiths GL, Goldenberg DM, Jones AL, Hansen HJ. Radio-labeling antibodies and fragments with technetium and rhenium. Bioconj Chem 1992; 3:91–99.
Mather SJ, Ellsion D. Reduction mediated 99mTc labeling of monoclonal antibodies. J Nucl Med 1990; 31:692–697.
Vanderheyden JL, Su F-M, Venkatesan P, Beaumier P, Bugaj J, Fritzberg A. The chemistry of rhenium-186-labeled antibodies and F(ab)′ 2 fragments for RIT in animals and man [abstract]. J Nucl Med 1990; 31:823.
Fritzberg AR. Advances in 99mTc-labeling of antibodies. Nuklearmedizin 1987; 26:7–12.
Fritzberg AL, Berninger RW, Hadley SW, Wester DW. Approaches to radiolabeling antibodies for diagnosis and therapy of cancer. Pharm Res 1988; 5:325–334.
Deutsch E, Libson K, Vanderheyden J-L, Ketring AR, Maxon HR. The chemistry of rhenium and technetium as related to the use of isotopes of the elements in therapeutic and diagnostic nuclear medicine. Nucl Med Biol 1986; 13:465–477.
Bisunadan MM, Blower PJ, Clarke SEM, Singh J, Clarke SEM. Synthesis and characterization of [186Re]rhenium(V) dimercaptosuccinic acid: a possible tumor radiotherapy agent. Int J Appl Radiat Isotop 1991; 42:167–171.
Su F-M, Axworthy D, Galster J, Weiden P, Vanderheyden JL, Fritzberg A. Characterization of patients′ urinary catabolites from Re-186 radiolabeled monoclonal antibodies and fragments [abstract]. J Nucl Med 1989; 31:823.
Atcher RW, Friedman AM, Hines JJ. An improved generator for the production of 212pb and 212Bi from 224Ra. Int J Appl Radiat Isotop 1988; 39:283–286.
Gansow OA, Atcher RW, Link DC, Friedman AF, Seevers RH, Anderson W, Steinberg DA, Strand M. Generator produced bismuth-212 chelated to chemically modified monoclonal antibody for use in radiotherapy. In: Knapp FF Jr, Butler TA, eds. Radionuclide generators: new systems for nuclear medicine applications. Washington, D.C.: American Chemical Society Symposium Series 1984; 241:215–227.
Kozak RW, Atelier RW, Gansow OA, Firedman AM, Hines JJ, Waldmann TA. Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle emitting radionuclides as modalities for radioimmunotherapy. Proc Natl Acad Sci USA 1986; 83:474–479.
Ruegg CL, Anderson-Berg WT, Brechbiel, MW, Mirzadeh S, Gansow OA, Starnd M. Improved in vivo stability and tumor targeting of bismuth-labeled antibody. Cancer Res 1990; 50:4221–4226.
Gould KL, Goldstein RA, Mullani NA. Economic analysis of clinical positron emission tomography of the heart with rubidium-82. J Nucl Med 1989; 30:707–717.
Gould KL, Goldstein RA, Mullani NA. Non-invasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VIII. Clinical feasibility of positron cardiac imaging without a cyclotron using generator-produced rubidium-82. J Am Coll Cardiol 1986; 7:775–789.
Gould KL. PET perfusion imaging and nuclear cardiology. J Nucl Med 1991; 32:579–606.
Gennaro GP, Neirinckx RD, Bergner B, Muller WR, Waranis A, Haney TA, Barker SL, Loberg MD, Yarnais A. A radionuclide generator and infusion system for pharmaceutical quality rubidium-82. In: Knapp FF Jr, Butler TA, eds. Radionuclide generators — new systems for nuclear medicine applications. ACS Symposium Series, No. 242. Washington, D.C.: American Chemical Society; 1984:135–150.
Yano Y, Budinger TF, Cahoon JL, Huesman RH. An automated microprocessor-controlled Rb-82 generator for positron emission tomography studies. In: Knapp FF Jr, Butler TA, eds. Radionuclide generators — new systems for nuclear medicine applications, ACS Symposium Series, No. 242. Washington, D.C.: Amercian Chemical Society; 1984:97–122.
Waters SL, Coursey BM, eds. The strontium-82/rubidium-82 generator. In: Int J Appl Radiat Isotop 1987;38 (special issue).
Brihaye C, Guillaume M, Cogneau M. Distribution coefficients of Sr and Rb ions on various adsorbents in view to achieving a Sr-Rb generator for medical use. Radiochem Radioanal Lett 1981; 48:157–164.
Neirinckx RD, Kronauge JF, Gennaro GP, Loberg MD. Evaluation of inorganic adorbents for the rubidium-82 generator: I. Hydrous SnO2. J Nucl Med 1982; 23:245–249.
Brihaye C, Guillaume M, O'Brien HA Jr, Raets D, de Landsheere C, Rigo P. Preparation and evaluation of a hydrous tin (IV) oxide 82Sr/82Rb generator system for continuous elution. Int J Appl Radiat Isotop 1987; 38:213–217.
Ramamoorthy N, Pao PJ, Watson JA. Preparation of a 62Zn-62Cu generator and of 61Cu following alpha particle irradiation of a nickel target. Radiochem Radioanal Lett 1981; 46:371–380.
Riley RJ, Tilbury RS. Production of zinc-62 by helium-3 bombardment of nickel. Int J Appl Radiat Isotop 1981; 32:60–61.
Robinson GD, Jr., Lee AW. A short-lived generator-produced, positron emitting radionuclide for radiopharmaceuticals. J Nucl Med 1976; 17:559.
Robinson GD Jr, Zielinsky FW, Lee AW. The zinc-62/copper-62 generator. A convenient source of copper-62 for radiopharmaceuticals. Int J Appl Radiat Isotop 1980; 31:111–116.
Thakur ML, Nunn AD. Preparation of carrier-free zinc-62 for medical use. Radiochem Radioanal Lett 1969; 2:301–305.
Nierinckx RD. Excitation function for the 62Zn bleomycin. Int J Appl Radiat Isotop 1977; 28:808–809.
Yano Y, Budinger TF. Cyclotron produced Zn-62: its possible use in prostrate and pancreas scanning as a Zn-62 amino acid chelate. J Nucl Med 1977; 18:815–821.
Green MA. A potential copper radiopharmaceutical for imaging the heart and brain: copper-labelled pyruvaldehyde bis(N4-methylthiosemicarbazone). Nucl Med Biol 1987; 14:59–61.
Green MA, Klippenstein DL. Copper(II)bis-(thiosemicarbazone) complexes as potential tracers for evaluation of cerebral and myocardial blood flow with PET. J Nucl Med 1988; 29:1549–1559.
Green MA, Mathias JC, Welch MJ, McGuire AH, Perry D, Fernandez-Rubio F, Perlmutter JS, Raichle ME, Bergmann SR. Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemi-carbazonato)copper(II): synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion. J Nucl Med 1990; 31:1989–1996.
Barnhardt AJ, Voorhees WD, Green MA. Correlation of Cu(PTSM) localization with regional blood flow in the dog kidney [abstract]. J Nucl Med 1990; 31:914.
Mathias CJ, Welch MJ, Green MA, Perry DJ, McGuire AH, Zhu X, Connett JM. Copper PTSM measures tumor blood flow too [abstract]. J Nucl Med 1990; 31:909.
Mirzadeh S, Lambrecht RM. Radiochemistry of germanium. J Radioanalyt Nucl Chem 1994 (in press).
Loc'h C, Mazière B, Comar D. A new generator for ionic gallium-68. J Nucl Med 1980; 21:171–173.
Mathias CA, Kung HF, Budinger TF, Wong PJ, Coxson PG, Brennan KM. Evaluation of [Ga-68]BAT TECH as a myocardial perfusion agent for PET [abstract]. J Nucl Med 1991; 32:974.
Paras P, Thiessen JW. Single-photon ultrashort-lived radionuclides. Proceedings of the Symposium held in Washington, D.C., 9–10 May 1983: U.S. Department of Energy. National Technical Information Service. CONF-830504 (DE 83017017);1985.
Franken PR, Dobbeleir A, Ham HR, Brihaye C, Guillaume M, Knapp FF Jr, Vandevivere J. Ultrashort-lived iridium-191m from a new carbon-based generator system for left ventricular first-pass angiocardiography. J Nucl Med 1989;30:1025–1031.
Franken PR, Dobbeleir AA, Ham HR, Ranquin R, Lieber S, Van Den Branden F, Van Den Heuvel P, Brihaye C, Guillaume M, Knapp FF Jr, Vandevivere J. Discrepancy between myocardial perfusion and regional wall motion at rest and during exercise in patients with coronary artery disease. Nucl Med Commun 1991; 12:473–484.
Guillaume M, Czichosz R, Richard P, Fagard E. Krypton-81m generator for ventilation and perfusion. Bull Soc Roy Liège 1983; LII:213–281.
Clark JC, Horlock PL, Watson IA. Krypton-81m generators. Radiochem Radioanal Lett 1976; 25:245–253.
Clark JC, Buckingham PD. Short-lived gases for clinical use. London: Butterworth, 1975.
Philip MS, Ramsey CI, Ma JM, Lamb JF. A Rr-81/Kr-81m perfusion generator. In: Knapp IF, Butler TA, eds. Radionuclide generators — new systems for nuclear medicine applications. ACS Symposium Series, No. 242. Washington, D.C.: Amercian Chemical Society; 1984:67–76.
Guillaume M, Brihaye C. Generators for short-lived gamma and positron emitting radionuclides: current status and prospects. Nucl Med Biol 1986; 13:89–100.
Janssen AGM, de Goeij JJM, Witsenboer AJ, Van Den Broek JFCM. Improved version of the wetted-paper 81Rb/81-Kr generator. Influence of porous capillary spreading and diffusion on the performance. Int J Appl Radiat Isotop 1990; 41:847–855.
Fazio F, Nardini M, Fieschi C, Forli C. Assessment of regional cerebral blood flow by continuous carotid infusion of krypton-81m. J Nucl Med 1977; 18:962–966.
Bett R, Cunningham JG, Sims HE, Willis HH, Dymond DS, Flatman W, Stone DL, Elliot AT. Preparation and characteristics of a 195mHg/195mAu generator for first-pass angiography. In: Knapp FF Jr, Butler TA, eds. Radionuclide generators —new systems for nuclear medicine applications, ACS Symposium Series, No. 242. Washington, D.C.: American Chemical Society; 1984:35–50.
Bett R, Cunningham JG, Sims HE, Willis HE, Dymond DS, Flatman W, Stone DL, Elliot AT. Development of the 195mHg/195mAu generator for first-pass radionuclide angiography of the heart. Int J Appl Radiat Isotop 1983; 34:959–963.
Panek KJ, Lindmeyer J, ven der Vlugt HC. A new generator for production of short-lived Au-195m radioisotope. In: Knapp FF Jr, Butler TA, eds. Radionuclide generators — new systems for nuclear medicine applications, ACS Symposium Series, No. 242. Washington, D.C.: American Chemical Society; 1984:3–22.
Panek KJ, Linderyer J, Van Der Vlught H. An improved 195mHg/195mAu generator. In: Parras P, Thiessen JW eds. Single-photon ultrashort-lived radionuclides. Proceedings of the Symposium held in Washington, D.C., 9–10 May 1983. U.S. Department of Energy. National Technical Information Service. CONF-830504 (DE 83017017); 1985:202–214.
Brihaye C, Guillaume M, Lavi N, Cogneau M. Development of a reliable Hg-195m→Au-195m generator for the production of Au-195m, a short-lived nuclide for vascular imaging. J Nucl Med 1982; 23:1114–1120.
Brihaye C, Guillaume M. 195Au biokinetics and dosimetry. Eur J Nucl Med 1990; 16:369–371.
Mena I. The role of ultrashort-lived radionuclides in cardiovascular studies: 195mAu ventriculography and simultaneous 201T1 myocardial imaging. In: Paras P, Thiessen JW eds. Single-photon ultrashort-lived radionuclides. Proceedings of the Symposium held in Washington, D.C., 9–10 May 1983, U.S. Department of Energy. National Technical Information Service. CONF-830504 (DE 83017017); 1985:19–29.
Wagner RK, Schad N, Bontenbal B. Combined regional functional and metabolic parametric imaging of the heart with gold-195m and iodine-123-labeled IPPA using a multi-crystal camera. NucCompact — Eur/Am Commun Nucl Med 1990; 21:118–121.
Yano Y, Anger HO. Ultra short lived radioisotopes for visualizing blood vessels and organs. J Nucl Med 1968; 9:1–6.
Treves S, Cheng C, Samuel A, Lambrecht R, Banchyk B, Norwood W. Iridum-191m angiocardiography for the detection and quantification of left-to-right shunting. J Nucl Med 1980; 21:1151–1157.
Treves S, Fyler D, Fujii A, Kuruc A. Low radiation iridium-191m radionuclide angiography: detection and quantification of left-to-right shunts in infants. J Pediatr 1982; 101:210–215.
Heller GV, Treves ST, Parker JA, Duke LA, O'Brien GM, Davis RT, Fitzgibbon C, Packard AB. Comparison of ultrashort-lived iridium-191m and 99mTc for first pass radionuclide angiocardiographic evaluation of left to ventricular function in adults. J Am Coll Cardiol 1986; 7:1295–1301.
Cheng C, Treves S, Samuel A, Davis MA. A new osmium-191/iridium-191m generator. J Nucl Med 1980; 21:1169–1176.
Packard AB, O'Brien GM, Treves S. The development of an 191Os/191mIr generator using an osmium chelate parent complex. I. trans-Dioxobismalonatoosmate(VI). Nucl Med Biol 1986; 13:519–526.
Packard AB, Treves S, O'Brien GM. An osmium-191/iridium-191m generator using an oxalate osmate parent complex. J Nucl Med 1987; 28:1571–1576.
Brihaye C, Butler TA, Knapp FF Jr. The Os-191/Ir-191m generator for clinical use. I. Evaluation of potential adsorbents. J Radioanal Chem Nucl Chem 1986; 102:399–411.
Brihaye C, Butler TA, Knapp FF Jr, Guillaume M. A new osmium-191/iridium-191m radionuclide generator system using activated carbon. J Nucl Med 1986; 27:380–387.
Brihaye C, Guillaume M, Butler TA, Knapp FF, Jr. Evaluation of the reactor production of osmium-191 for use in the carbon-based Os-191/Ir-191m medical generator. In: Seminar on radionuclide generators, Vienna, Austria, 13–17 October 1986. Symposium, IAEA-SR-131/08, 1986.
Callahan RJ, Fund D, Dragotakes SC, Rice DE, Goodman MM, Barlai-Kovach M, Hunford M, Knapp FF Jr, Strauss HW. Evaluation of the Os-191/Ir-191m generator in the constant infusion mode [abstract]. J Nucl Med 1986; 27:916.
Issachar D, Abrashkin S, Weiniger J, Zemach D, Lubin E, Hellman C, Tramper D. Osmium-191/iridium-191m generator based on silica gel impregnated with tridodecylmethylammonium chloride. J Nucl Med 1989; 30:538–541.
Hellman C, Zafrir N, Shimoni A, Issachar D, Trumper J, Abrashkin S, Lubin E. Evaluation of ventricular function with first-pass iridium-191m radionuclide angiography. J Nucl Med 1989; 30:450–457.
Guillaume M, Brihaye C, Redote R, Zicot M, Knapp FF Jr. Iridium-191m: a new radiotracer for arterioscintigraphy [abstract]. J Nucl Med 1988; 29:841.
Neirinckx RD, Tramper J, LeBlanc A, Johnson PC. Evaluation of adsorbents for the Ta-178 generator. In: Knapp FF Jr, Butler TA, eds. Radionuclide generators — new systems for nuclear medicine applications, ACS Symposium Series, No. 242. Washington, D.C.: American Chemical Society; 1984:151–168.
Lacy JL, Verani MS, Ball ME, Boyce TM, Gibson RW, Roberts R. First-pass radionuclide angiography using a multiwire gamma camera and tantalum-178. J Nucl Med 1988; 29:293–301.
Lacy JL, Ball ME, Verani MS, Wiles HB, Babich JW, LeBlanc AD, Stabin M, Bolomey L, Roberts R. An improved tungsten-178/tantalum-178 generator system for high volume clinical applications. J Nucl Med 1988; 29:1526–1538.
Layne WW, Lacy JL. Tantalum-178-labeled radiopharmaceutical synthesis via the intermediate tantalum pentachloride —a potential myocardial perfusion agent. In: Emran AM, ed. New trends in radiopharmaceutical synthesis, quality assurance and regulatory control. Plenum Press: New York; 1991:213–225.
Steinkruger FJ, Wanek PM, Moody DC. Cadmium-109/silver-109m biomedical generator. International Atomic Energy Agency. Seminar on radionuclide generator technology. Vienna, Austria, 13–17 October 1986. Symposium, IAEA-SR131/08, 1986.
Mausner L. The in vivo generator. Presented at the Division of Nuclear Chemistry and Technology, 204th American Chemical Society National Meeting, 23–28 August 1992.
Ma D, Jurisson SS, Ehrhardt GJ, et al. Development of the Dy-166/Ho-166 in vivo generator for radionuclide radiotherapy [abstract]. J Nucl Med 1993; 34:231P.
Mirzadeh S, DiBartolo N, Smith SV, et al. Dysprosium-166/holmium-166 generator. In: Proceedings, tenth international symposium on radiopharmaceutical chemistry, Kyoto, Japan, 25–28 October 1993:276–278.
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Correspondence to: RE Knapp, Jr.
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Knapp, F.F.(., Mirzadeh, S. The continuing important role of radionuclide generator systems for nuclear medicine. Eur J Nucl Med 21, 1151–1165 (1994). https://doi.org/10.1007/BF00181073
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DOI: https://doi.org/10.1007/BF00181073