Skip to main content
Log in

Radiolabeling with technetium-99m to study high-capacity and low-capacity biochemical systems

  • Occasional Survey
  • Published:
European Journal of Nuclear Medicine Aims and scope Submit manuscript

Abstract

After a brief review of the history of the development of technetium-99m-labeled radiopharmaceuticals, the use of technetium chelates in high-capacity systems is discussed. The latter are used in the study of five organ systems, the kidneys, liver, bone, brain, and heart. The chemical characterization of99mTc complexes is also reviewed, followed by discussion of the various approaches to the labeling of proteins with direct labeling, the preformed chelate approach, and the antibody chelator conjugate approach. Thereafter, the labeling of biochemicals with99mTc for use with easily saturated sites, e.g., receptors and enzymes, is considered. Finally, attention is given to factors that affect the preparation of high specific activity, high affinity99mTc-labeled biochemicals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Segre E. The adventurous history of the discovery of technetium. In:Technetium in chemistry and nuclear medicine, vol. 2. 1986:1–10.

  2. Segre E, Seaborg GT. Discovery of technetium.Phys Rev, 1938; 54: 772.

    Google Scholar 

  3. Anders E.The radiochemistry of technetium. National Academy of Sciences, National Research Council, National Technical Information Service, 1960.

  4. Richards P. A survey of the production at Brookhaven National Laboratory of radioisotopes for medical research. In: V. congresso nucleare “Rome”, comitato nazional ricerche nucleari, 1960;2: 223–244.

  5. Harper PV, Beck R, Charleston D, Lathrop KA. Optimization of a scanning method using99mTc.Nucleonics 1964;22: 50–54.

    Google Scholar 

  6. Harper PV, Andros G, Lathrop KA.Semiannual report to the Atomic Energy Commission. ACRH, 1962;18: 76–87.

    Google Scholar 

  7. Harper PV, Lathrop KA, Richards P. A radiocolloid of99mTc.J Nucl Med 1964;5: 382.

    Google Scholar 

  8. Richards P, Atkins HL,Proceedings of the 7th Annual Meeting of the Japanese Society of Nuclear Medicine. Jpn J Nucl Med 1968;7: 165–170.

    Google Scholar 

  9. Richards P, Tucker WD, Srivastava SC. Introduction; technetium-99m: an historical perspective.Int J Appl Radiat Isot, 1982;33: 793–799.

    Google Scholar 

  10. Eckelman WC, Richards P. Instant99mTc-DTPA.J Nucl Med 1970;11: 761.

    Google Scholar 

  11. The nuclear medicine market. 1988 New York: Frost and Sullivan.

  12. Shellabarger C, Richards P.Bulletin of the Medical Department. Brookhaven National Laboratory, July 1960.

  13. Atkins HL, Richards P, Schiffer L. Scanning of liver, spleen, and bone marrow with colloidal 99m-technetium.Nucl Appl 1966;2: 27–32.

    Google Scholar 

  14. McAfee JG, Stern HS, Fueger CF, Baggish MS, Holzman GB, Zolle I.99mTc-labeled serum albumin for scintillation scanning of the placenta.J Nucl Med 1964;5: 936–946.

    Google Scholar 

  15. Taplin GV, Poe ND. A dual lung-scanning technic for evaluation of pulmonary function.Radiology 1965;85: 365–368.

    Google Scholar 

  16. Stern HS, McAfee JG, Subramanian G. Preparation, distribution, and utilization of technetium-99m-sulfur colloid.J Nucl Med 1966;7: 665–675.

    Google Scholar 

  17. Harper P, Lathrop KA, Gottschalk A. Pharmacodynamics of technetium-99m in radioactive pharmaceuticals.USAEC Technical Information Service, 1966:335–358.

  18. Gwyther MM, Field EO. Aggregated99mTc-labeled albumin for lung scinti-scanning.Int J Appl Radiat Isot 1966;17: 485–486.

    Google Scholar 

  19. Eckelman WC, Richards P. Instant99mTc compounds.Nucl Med 1971;10: 245–251.

    Google Scholar 

  20. Eckelman WC, Meinken G, Richards P.99mTc human serum albumin.J Nucl Med 1971;11: 707–710.

    Google Scholar 

  21. Eckelman WC, Richards P, Hauser W, Atkins H. Technetium-labeled red blood cells.J Nucl Med 1971;12: 22–24.

    Google Scholar 

  22. Subramanian G, McAfee JG. A new complex of99mTc for skeletal imaging.Radiology, 1971;99: 192–196.

    Google Scholar 

  23. Rhodes BA, Stern HS, Buchanan JA, et al. Lung scanning with99mTc microspheres.Radiology 1971;99: 613–621.

    Google Scholar 

  24. Yano Y, McRae J, Van Dyke DC, et al. Technetium-99m-labeled stannous ethane-1-hydroxy-1-diphosphonate: a new bone scanning agent.J Nucl Med 1973;14: 73–78.

    Google Scholar 

  25. Lin TH, Khentigan A, Winchell HS. A99mTc chelate substitute for organ radiomercurial renal agents.J Nucl Med 1974;15: 34–35.

    Google Scholar 

  26. Subramanian G, McAfee JG, Blair RJ, Kallfelz FA, Thomas FD. Technetium-99m-methylene diphosphonate — a superior agent for skeletal imaging: comparison with other technetium complexes.J Nucl Med 1975;16: 744–755.

    Google Scholar 

  27. Loberg MD, Cooper M, Harvey E, Callery P, Faith W. Development of new radiopharmaceuticals based on N-substitution of iminodiacetic acid.J Nucl Med 1976;17: 633–638.

    Google Scholar 

  28. Winston BW, Subramanian G, Gagne GM, Henderson RW, McAfee JG, Hall RC, Grossman ZD. Experimental and clinical trials of new99mTc hepatobiliary agents.Radiology 1978;128: 793.

    Google Scholar 

  29. Nunn AD, Loberg MD, Conley RA. A structure-distribution relationship approach leading to the development of Tc-99m mebrofenin; an improved cholescintigraphic agent.J Nucl Med 1983;24: 423–430.

    Google Scholar 

  30. Bevan JA, Tofe AJ, Benedict JJ, Francis MD, Barrett BL. Tc-99m HMDP (hydroxymethylenediphosphonate): a radiopharmaceutical for skeletal and acute myocardial infarct imaging. I. Synthesis and distribution in animals.J Nucl Med 1980;21: 961.

    Google Scholar 

  31. Neirinckx RD, Canning LR, Piper IM, Nowotnik DP, Pickett RD, Holmes RA, Volkert WA, Forster AM. Technetium-99md,I-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion.J Nucl Med 1987;28: 191–202.

    Google Scholar 

  32. Volkert WA, Hoffman TJ, Segrr TM, et al.99mTc-propylene amine oxime (Tc-99m-PnAO): a potential brain radiopharmaceutical.Eur J Nucl Med 1984;9: 511–516.

    Google Scholar 

  33. Holman BL, Jones AG, Lister-James J, et al. A new Tc-99mlabeled myocardial imaging agent, hexakis (t-butylisonitrile)technetium (I) (Tc-99m TBI). Initexperience in the human.J Nucl Med 1984;25: 1350–1355.

    Google Scholar 

  34. Taylor A, Eshima D, Fritzberg AR, Christian PE, Kasina S. Comparison of iodine-131-OIH and technetium-99m-MAG3 renal imaging in volunteers.J Nucl Med 1986;27: 795–803.

    Google Scholar 

  35. Treher EN, Gougoutas J, Malley M, Nunn AD, Unger SE. New Technetium radiopharmaceuticals: boronic acid adducts of vicinal dioxime complexes.J Label Comp Radiopharm 1986;23: p 118.

    Google Scholar 

  36. Burch WM, Sullivan PJ, McLaren CJ. Technegas — a new ventilation agent for lung scanning.Nucl Med Commun 1986;7: 865–871.

    Google Scholar 

  37. Walovitch RC, Hilly TC, Garrity ST, Cheesman EH, Burgess BA, O'Leary DH, Watson AD, Ganey MV. Characterization of technetium-99m-L,L-ECD for brain perfusion imaging. Part 1. Pharmacology of technetium-99m ECD in nonhuman primates.J Nucl Med 1989;30: 1892–1901.

    Google Scholar 

  38. Kelly JD, Forster AM, Higley B, et al. Technetium-99m-tetrofosmin as a new radiopharmaceutical for myocardial perfusion imaging.J Nucl Med 1993;34: 222–227.

    Google Scholar 

  39. Arnold RW, et al. Comparison of99mTc complexes for renal imaging.J Nucl Med 1975;16: 357–367.

    Google Scholar 

  40. Fleay RF.99mTc-labeled EDTA for renal scanning.Australas Radiology 1968;12: 265–267.

    Google Scholar 

  41. Hauser W, Atkins HL, Nelson KG, et al. Technetium-99m DTPA: a new radiopharmaceutical for brain and kidney scanning.Radiology 1970;94: 679–684.

    Google Scholar 

  42. Lebowitz E, Atkins HL, Hauser W, et al.99mTc-gelatin: a “compound” with high renal specificity.Int J Appl Radiat Isot 1971;22: 786–789.

    Google Scholar 

  43. Halpern SE, Tubis M, Ensow SJ, et al.99mTc-penicillamine-acetazolamide complex, a new renal scanning agent.J Nucl Med 1972;13: 45–50.

    Google Scholar 

  44. Halpern SE, Tubis M, Golden M, et al.99mTcPAC; a new renal scanning agent. II. Evaluation in humans.J Nucl Med 1972;13: 723–728.

    Google Scholar 

  45. Winchell HS, Lin M, Shipley B, et al. Localization of polypeptide caseidin in the renal cortex: a new radioisotope carrier for renal studies.J Nucl Med 1971;12: 678–682.

    Google Scholar 

  46. Kountz SL, Yeh SH, Wood J, et al. Technetium-99m(V)-citrate complex for estimation of glomerular filtratrion rate.Nature 1967;215: 1397–1399.

    Google Scholar 

  47. Fliegel CP, Dewanjee MK, Holman LB.99mTc tetracycline as a kidney and gallbladder imaging agent.Radiology 1974;110: 407–412.

    Google Scholar 

  48. Chervu LR, Blaufox MD. Renal radiopharmaceuticals—an update.Seminars in Nucl. Med. 1982;12: 224–245.

    Google Scholar 

  49. Charamaza O, Budikova M. Herstellungsmethode eines99mTc-zinn-komplexes fur die Nierenszintigraphie.J Nucl Med 1969;8: 301.

    Google Scholar 

  50. Lichte H, Hor G. Nierenszintigraphie mit Tc-99m penicillamine. Fortschr Geb RontgenstrNuklearmed 1975;122: p. 119.

    Google Scholar 

  51. Yokoyama A, Saji H, Tanaka H, et al. 99Tcm chemical state in99Tcm labeled radiopharmaceuticals. I. Preparation and biological behavior of 99Tcm-penicillamine complex with a low hydrolyzed99Tcm state.Int J Nucl Med Biol 1978;5: 45–49.

    Google Scholar 

  52. Ikeda I, Inoue O, Uchida J, et al. New renal scanning agents of Tc-99m compounds.World Congress Nucl Med 1974.

  53. Subramanian G, Singh MV, Chander J, Singh B. Tc-99m-Sn-acetylcysteine: a new renal scanning agent.Eur J Nucl Med 1976;1: 243–245.

    Google Scholar 

  54. Johannson B, Syhre P, Spies H. Analytische Untersuchungen zur markierung von Cystein und Glutathion mit Technetium-99m.Jahresbericht des Zentralinstitutes fur Kernforschung Rossendorf Zfk 1976;312: 53.

    Google Scholar 

  55. Oginski M, Rembelska M. Tc-99m-unithiol complex a new pharmaceutical for kidney scintigraphy.J Nucl Med 1976;15: 282–286.

    Google Scholar 

  56. Johannson B, Spies H.Chemie und Radiopharmakologie von Technetium Komplexen. Dresden: Academic der Wissenschaften der DDR, 1981.

    Google Scholar 

  57. Troutner DE, Simon J, Ketring AR, et al. Complexing of Tc99m with cyclam: concise communication.J Nucl Med 1980;21: 443–448.

    Google Scholar 

  58. Davison A, Sohn M, Orvig C, et al. A tetradentate ligand designed specifically to coordinate technetium.J Nucl Med 1979;20: 641.

    Google Scholar 

  59. Jones AG, et al. Chemical in vivo studies of the anion oxo [N,N′-ethylenebis(2-mercaptoacetimido)]. technetate(V).J Nucl Med 1982;23: 801–809.

    Google Scholar 

  60. Yokoyama A, Terauchi Y, Horiuchi K. Technetium-99m-kethoxal-bis (thiosemicarbazone) an uncharged complex with a tetravalent99mTc state and its excretion into the bile.J Nucl Med 1976;17: 816–819.

    Google Scholar 

  61. Verbruggen A, et al. Synthesis and renal excretion characteristics of the four stereoisomers present in99mTc bis(mercaptoacetyl)-22-diaminopropanoate (Tc99m-CO2-DADS).J Nucl Med 1985;26: 1985.

    Google Scholar 

  62. Fritzberg AR, Kasina S, Dshima D, Johnson DL. Synthesis and biological evaluation of technetium-99m-MAG3 as a hippuran replacement.J Nucl Med 1986;27: 111–116.

    Google Scholar 

  63. Tubis M, Krishnamurthy GT, Endow JS, Blahd WH. 99m Tc-penicillamine a new cholescintigraphic agent.J Nucl Med 1972;13: 652–654.

    Google Scholar 

  64. Baker RJ, Bellen JC, Ronai PM. Technetium 99m-pyridoxylideneglutamate: a new hepatobiliary radiopharmaceutical.J Nucl Med 1975;16: 720.

    Google Scholar 

  65. Dugal P, Eikman EA, Natarajan TK, Wagner HW Jr. A quantitative test for gallbladder function.J Nucl Med 1972;13: 428.

    Google Scholar 

  66. Lin TH, Khentigan A, Winchell HS. A99mTc-labelled replacement for131I-rose bengal in liver and biliary tract studies.J Nucl Med 1974;15: 613–615.

    Google Scholar 

  67. Hunt FC, Maddalena DJ, Yeates MG. Technetium-99m-6 mercaptopurine a new radiopharmaceutical for cholescintigraphy. In:Recent advances in nuclear medicine. Proceedings of First World Congress for Nuclear Medicine Tokyo 1974.

  68. Callery PS, Faith B, Loberg MD, et al. Tissue distribution of technetium-99m and carbon-14 labeledN-(26-dimethylphe-nylcarbamylmethyl) imino-diacetic acid.J Med Chem 1976;19: 962–964.

    Google Scholar 

  69. Burns HD, Sowa DT, Marzilli LG. Improved synthesis ofN(26-dimethylphenylcarbamoylmethyl) iminodiacetic acid and analogs.J Pharm Sci 1978;67: 1434–1436.

    Google Scholar 

  70. Wistow BW, Subramanian G, Van Heertum RL, et al. An evaluation of 99mTc-labeled hepatobiliary agents.J Nucl Med 1977;18: 455–461.

    Google Scholar 

  71. Burns HD, Worley P, Wagner HN Jr, et al. In: Heindel N, ed.Design of technetium radiopharmaceuticals. Chemistry of radiopharmaceuticals. New York: Masson; 1978:269–289.

    Google Scholar 

  72. Van Wyke AJ, Fourie PJ, Van Zyl WH, et al. Synthesis of five new99mTc-HIDA isomers and comparison with99mTc-HIDA.Euro J Nucl Med 1979;4: 445–148.

    Google Scholar 

  73. Molter M, Kloss G. Studies of pharmacokinetics of various Tc-99m-IDA derivatives J. Label Compd Radiopharm 1981; 18:196–197.

    Google Scholar 

  74. Nunn AD. Preliminary structure-distribution relationships of99mTc hepatobiliary agents. I. Protein binding of HIDA's. J. Label Compd Radiopharm 1981;18: 155–156.

    Google Scholar 

  75. Nunn AD, Loberg MD. Hepatobiliary agents. In: Spencer RP, ed.Radiopharmaceuticals: structure-activity relationships. New York: Grime & Stratton; 1981: 539.

    Google Scholar 

  76. Subramanian G, McAfee JG, Bell EG, et al.99mTc-labeled polyphosphate as a skeletal imaging agent.Radiology 1972;102: 701–704.

    Google Scholar 

  77. Cohen Y, et al. Use of technetium 99m-labelled sodium pyrophosphate in skeletal scintigraphy.C R Acad Sci Hebd Seances Acad Sci D 1972;275: 1719–1721.

    Google Scholar 

  78. Bevan JA, Tofe AJ, Benedict JJ. Tc-99m HMDP (hydroxy-methylene diphosphonate): a radiopharmaceutical for skeletal and acute myocardial infarct imaging. II. comparison of Tc-99m hydroxymethylene diphosphonate (HMDP) with other technetium-labeled bone-imaging agents in a canine model.J Nucl Med 1980;21: 967–970.

    Google Scholar 

  79. Subramanian G, McAfee JG, Blair RJ, et al. Technetium-99m labelled stannous imidodiphosphate a new radiodiagnostic agent for bone scanning: comparison with other99mTc complexes.J Nucl Med 1975;16: 1137–1143.

    Google Scholar 

  80. Jones A.G, Francis MD, Davis MA. Bone scanning: radionuclide reaction mechanisms.Semin Nucl Med 1976;6: 3–18.

    Google Scholar 

  81. Davis MA, Jones AL. Comparison of99mTc-labeled phosphate and phosphonate agents for skeletal imaging.Semin Nucl Med 1976;6: 19–31.

    Google Scholar 

  82. Johnson LL, Seldin DW, Muschel M, et al. Comparison of planar SQ 30217 and TI-201 myocardial imaging with coronary anatomy [abstract].Circulation 1987; 76: 217.

    Google Scholar 

  83. Seldin DW, Johnson LL, Blood DK, et al. Myocardial perfusion imaging with technetium-99m SQ 30217: comparison with thallium-201 and coronary anatomy.J Nucl Med 1989;30: 312–319.

    Google Scholar 

  84. Meerdink DJ, Thuber M, Savage S, et al. Comparative myocardial extraction of two technetium labeled boron oxime derivatives (SQ 30217 SQ 32014) and thallium.J Nucl Med 1988;29: 972.

    Google Scholar 

  85. Narra RK, Nunn AD, Kuczynski BL, et al. A neutral99mTc complex for myocardial imaging.J Nucl Med 1989;30: 1830–1837.

    Google Scholar 

  86. Kim AS, Akers MS, Faber TS, et al. Dynamic myocardial perfusion imaging with Tc-99m-teboroxime in patients; comparison with thallium-201 and arteriography [abstract].Circulation 1990; 82: 321.

    Google Scholar 

  87. Gewirtz H. Differential myocardial washout of technetium-99m teboroxime: mechanism and significance.J Nucl Med 1992;32: 2009–2011.

    Google Scholar 

  88. Leppo JA, DePuey EG, Johnson LL. A review of cardiac imaging with sestamibi and teboroxime.J Nucl Med 1991;32: 2012–2022.

    Google Scholar 

  89. Iskandrian L, Schelbert HR. Myocardial viability assessment.JNucl Med 1994. 4 (Suppl).

  90. Winchell HS, Horst WD, Braun L, et al.N-Isopropyl[123I]iodoamphetamine: single pass brain uptake and washout binding to brain synaptosomes and localization in dog and monkey brain.J Nucl Med 1980;21: 947–952.

    Google Scholar 

  91. Neirinckx RD, Burke JF, Harrison RC, et al. The retention mechanism of99mTc-HMPAO; intracellular reaction with glutathione.J Cereb Blood Flow Metab 1988;8: S4-S12.

    Google Scholar 

  92. Roth CA, Hoffman TJ, Corlija M, Volkert WA, Holmes RA. The effect of ligand structure on glutathione-mediated decomposition of propylene amine oxime derivatives.Int J Radiat Appl Instrum. [B] 1992;19: 783–790.

    Google Scholar 

  93. Vallabhajosula S, Zimmerman RE, Picard M, et al. Technetium-99m ECD: a new brain imaging agent: in vivo kinetics and biodistribution studies in normal human subjects.J Nucl Med 1989;30: 599–604.

    Google Scholar 

  94. Peacock RD, inComprehensive inorganic chemistry. Oxford: Permagon 1973: 877–903.

    Google Scholar 

  95. Rouschias G, Recent advances in the chemistry of rhenium.Chem Rev 1974;74: 531–566.

    Google Scholar 

  96. Steigman J, Meinken G, Richards P. Reduction of pertechnetate-99 by stannous chloride. I. Stochiometry of the reaction in hydrochloric acid in a citrate buffer and in a DTPA buffer.Int J Appl Radiat Isot 1975;26: 601–609.

    Google Scholar 

  97. Steigman J, Hwang L, Srivastava S. Complexes of reduced technetium-99 with polyhydric compounds.J Label Compd. Radiopharm 1977;13: 160.

    Google Scholar 

  98. Steigman J, Hwang L, Solomon NA, Kan T. Cysteine and albumin complexes of technetium-99 and technetium-99m.J Label Compd. Radiopharm 1977;13: 162.

    Google Scholar 

  99. DePamphilis BV, Jones AG, Davis MA. Preparation and crystal structure of oxotechnetium bis (thiomercaptoacetate) and its relationship to radiopharmaceuticals labeled with99mTc.J Am Chem Soc 1978;78: 5570–5571.

    Google Scholar 

  100. Smith JE, Byrne EF, Colton FA, Sekutowski JC. A thiol complex of technetium pertinent to radiopharmaceutical use of99mTc.J Am Chem Soc 1978;78: 5571–5572.

    Google Scholar 

  101. Siripaisarnpipat S, Schlemper EO. Preparation spectra and crystal structures of two rhodium (III) complexes with short intramolecular hydrogen bonds.Inorganic Chem 1984;23: 330–334.

    Google Scholar 

  102. Vassian EG, Murmann RK. Aromatization of an aliphatic amine oxime nickel (II) complex by molecular oxygen.Inorganic Chem 1967;6: 2043–2046.

    Google Scholar 

  103. Troutner DE, Volkert WA, Hoffman TJ, Holmes RA. A neutral lipophilic complex of99mTc with a multidentate amine oxime.Int J Appl Radiat Isot 1984;35: 467–470.

    Google Scholar 

  104. Fair CK, Troutner DE, Schlemper EO, Murmann RK, Hoppe ML. Oxo [3,3′-(1 3-propanediylidimino) his (3-methyl-2-butane oximato)(3-)-N,1N′,1N′,N′,N′′′) technetium V] [Tc O (C13H25-N402)].Acta Crystallogr Crystal Struct Commun 1984;C40 (Sect. C): 1544–1546.

    Google Scholar 

  105. Jurisson S, Schlemper EO, Troutner DE, Canning LR, Nowotnik DP, Neirinckx RD. Synthesis characterization and X-ray structural determinations of technetium (V)-oxo-tetra dentate amine oxime complexes.Inorg Chem 1986;25: 543–549.

    Google Scholar 

  106. Nunn AD, Feld T, Treher EN. Boronic acid adducts of technetium oxime complexes (BATOs), a new class of neutral complexes with myocardial imaging capabilities. United States Patent #4705849 1987.

  107. Linder K, Feld T, Juri PN, Nunn AD, Treher EN. A new technetium agent SQ 32 097 which can be used to assess cerebral blood flow.J Nucl Med 1987;28: 592.

    Google Scholar 

  108. Abrams MT, Davison A, Brodack JW, et al. The preparation of technetium (III) compounds in aqueous media.J Label Compd Radiopharm 1982;14: 1596.

    Google Scholar 

  109. Abrams MJ, Davison A, Jones AG, et al. Synthesis and characterization of hexakis (alkyl isocyanide) and hexakis (aryl isocyanide) complexes of technetium (I).Inorg Chem 1983;22: 2798–2800.

    Google Scholar 

  110. Nowotnik DP, Jurisson SS. Structure and stereochemistry in technetium coordination complexes. In: Steigman J, Eckelman WC, eds.The chemistry of technetium in medicine. National Academy Press; 1993: NAS-NS-3204 pp 111–180.

  111. Rhodes BA, Torvestaad DA, Burchiel SW, Austin RK. A kit for direct labeling of antibody and antibody fragments with Tc-99m.J Nucl Med 1980;21: 54.

    Google Scholar 

  112. Hawkins EB, Pant KD, Rhodes BA. Resistance of direct Tc-99m-protein bond to transchelation.Antibody Immuno Conj Radiopharm 1990;3: 17–25.

    Google Scholar 

  113. Pszona A, Sakowicz A. The influence of citrate ions on the radiochemical purity of 99mTc-human serum albumin.Int J Appl Radiat Isot 1981;32: 349–350.

    Google Scholar 

  114. Reno JM, Bottino BJ. Radiolabeled proteins especially antibodies and their preparation and use as diagnostic and therapeutic agents. European Pat. Appl. EP 237150 A2 1987.

  115. Pak KY, Labeling and stability of radiolabeled antibody fragments by a direct 99mTc-labeling method.Int J Radiat Appl Instrum [B] 1992;19: 669–677.

    Google Scholar 

  116. Bremer KH, Kuhlmann FL, Schwarz A, Steinstraesser A. Preparation of a technetium-99m-labeled organ-specific substance. European Pat. Appl. EP 271806 A21988.

  117. Feitsma RIJ, Blok D, Wasser MNJM, et al. A new method for technetium-99m-labeling of proteins with an application to clot detection with an antifibrin monoclonal antibody.Nucl Med Commun 1987;8: 771–777.

    Google Scholar 

  118. Blok D, Feitsma RIJ, Wasser MNJM, et al. A new method for protein labeling with technetium-99m.Nucl Med Biol 1989;16: 11–16.

    Google Scholar 

  119. Baldas J, Bonnyman J. Substitution reactions of99mTcNCl4. A route to a new class of99mTc radiopharmaceuticals.Int J Appl Radiat Isot 1985;36: 133–139.

    Google Scholar 

  120. Hwang LL-Y, Ronca N, Solomon NA, Steigman J. Complexes of technetium with polyhydric ligands.Int J Appl Radiat Isot 1985;36: 475–480.

    Google Scholar 

  121. Steigman J, Richards P. Chemistry of technetium as applied to radiopharmaceuticals. In: Subramanian G, et al., eds.Radiopharmaceuticals. Soc Nucl Med; 1975: 23–35.

  122. Thakur ML, DeFulvio J, Richard MD, Park CH. Technetium-99m labeled monoclonal antibodies: evaluation of reducing agents.Int J Radiat Appl Instrum [B] 1991;18: 227–33.

    Google Scholar 

  123. Thakur ML, DeFulvio JD. Technetium-99m-labeled monoclonal antibodies for immunoscintigraphy. Simplified preparation and evaluation.J Immunol Methods 1991;137: 217–224.

    Google Scholar 

  124. John E, Wilder S, Thakur ML. Structural perturbations of monoclonal antibodies following radiolabelling: in vitro evaluation of different techniques.Nucl Med Commun 1994;15: 24–28.

    Google Scholar 

  125. Hnatowich KJ, Mardirossian G, Roy S, et al. Pharmacokinetics of the FO23C4 anti-CEA antibody fragment labeled with technetium-99m and indium-111: a comparison in patients. Nucl Med Commun 1993: 52–63.

  126. Goedemans WT, Panek KJ, Ensing GJ, Delong MT. A new single method for labeling of proteins with99mTc by derivatization with 1-imino-4-mercaptobutyl groups. In: Nicolini M, Bandoli G, Mazzi U, eds.Technetium and rhenium in chemistry and nuclear medicine. Verona: Cortina International Raven;1990: 595–598.

    Google Scholar 

  127. Fritzberg AR, Abrams PG, Beaumier PL. et al. Specific and stable labeling of antibodies with technetium-99m with a diamide dithiolate chelating agent.Proc Natl Acad Sci USA 1988;85: 4025–4029.

    Google Scholar 

  128. Fritzberg AR, Berninger RW, Hadley SW, Wester DW. Approaches to radiolabeling of antibodies for diagnosis and therapy of cancer.Pharm Res 1988;5: 325–334.

    Google Scholar 

  129. Kasina S, Rao TN, Srinivasan A, et al. Development and biologic evaluation of a kit for performed chelate technetium-99m radiolabeling of an antibody Fab fragment using a dia mide dimercaptide chelating agent.J Nucl Med 1992;32: 1445–1451.

    Google Scholar 

  130. Breitz HB, Fisher DR, Weiden PL, Durham JS, Ratliff BA, Bjorn MJ, Beaumier PL, Abrams PG. Dosimetry of rhenium-186-labeled monoclonal antibodies: methods prediction from technetium-99m-labeled antibodies and results of phase I trials.J Nucl Med 1993;34: 908–917.

    Google Scholar 

  131. Linder KE, Wen MD, Nowotnik DP, et al. Technetium labeling of monoclonal antibodies with functionalized BATO's: 2.TcCl(DMG)3 CPITC labeling of B72.3 and NP-4 whole antibodies and NP-4 F(ab′)2.Bioconjugate Chem 1991;2: 407–414.

    Google Scholar 

  132. Franz J, Volkert WA, Barefield EK, Holmes RA. The production of technetium-99m-labeled conjugated antibodies using a cyclam-based bifunctional chelating agent.Nucl Med Biol 1987;14: 569–572.

    Google Scholar 

  133. Goodwin DA, Meares CF, McCall MJ, McTigue M, Chaovapong W. Pre-targeted immunoscintigraphy of murine tumors with indium-111-labeled bifunctional haptens.J Nucl Med 1988;29: 226–234.

    Google Scholar 

  134. Koch P, Mäcke HR.99mTc-labeled biotin conjugate in a tumor “pretargeting” approach with monoclonal antibodies.Angewandte Chemie 1992;31: 1507–1509.

    Google Scholar 

  135. Nock B, Evard F, Paganelli G, Mäcke HR.99mTcN4-Lys-biotin, a new biotin derivative useful for pretargeted avidin-biotin immunoscintigraphy: synthesis, radiochemistry and biological evaluation.J Nucl Biol Med 1994;38: 460–461.

    Google Scholar 

  136. Paik CH, et al. Factors influencing DTPA conjugation to antibodies via cyclic DTPA anhydride.J Nucl Med 1983;24: 1158–1163.

    Google Scholar 

  137. Baidoo KE, Scheffel U, Lever SZ.99mTc labeling of proteins: initial evaluation of a novel diamine dithiol bifunctional chelating agent.Cancer Res (Suppl) 1990: 150: 799s-803s.

    Google Scholar 

  138. Najafi A, Alauddin MM, Siegel ME, et al. Synthesis and preliminary evaluation of a new chelate N2S4 for use in labeling proteins with metallic radionuclides.Int J Radiat Appl Instrum [B] 1991;18: 179–185.

    Google Scholar 

  139. Arano Y, Yokoyama A, Furukawa T, Horiuchi K, Yahata T, Saji H, Sakahara H, Nakashima T. Technetium-99m-labeled monoclonal antibody with preserved immunoreactivity and high in vivo stability.J Nucl Med 1987;28: 1027–1033.

    Google Scholar 

  140. Schwartz DA, Abrams MJ, Hauser M, et al. Preparation of hydrazino-modified proteins and their use for the synthesis of99mTc-protein conjugates.Bioconjugate Chem 1991;2: 333–336.

    Google Scholar 

  141. Abrams MJ, Juweid M, tenKaate CI, Schwartz DA, Hauser MM, Gaul FE, Fucello AJ, Rubin RH, Strauss HW, Fischman AJ. Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection of rats.J Nucl Med 1990;31: 2022–2028.

    Google Scholar 

  142. Babich JW, Graham W, Barrow SA, Dragotakes SC, Tompkins RG, Rubin RH, Fischman AJ. Technetium-99m-labeled chemotactic peptides: comparison with indium-111-labeled white blood cells for localizing acute bacterial infections in rabbits.J Nucl Med 1993;34: 2176–2181.

    Google Scholar 

  143. Renault H, Henry R, Rapin J, Hegesippe M. Chelation de cations radioactifs par un polypeptide: la bleomycine. In:Radiopharmaceuticals and labeled compounds. Vienna: IAEA;1973: 7: 232–235.

    Google Scholar 

  144. Reba RC, Eckelman WC, Poulose KP, et al. Tumor-specific radiopharmaceuticals: radiolabeled bleomycin. In: Subramanian G, et al., eds.Radiopharmaceuticals. New York: Society of Nuclear Medicine; 1975: 464–473.

    Google Scholar 

  145. Richards P, Steigman J. Chemistry of technetium as applied to radiopharmaceuticals. In: Subramanian G, et al., eds.Radiopharmaceuticals. New York: Society of Nuclear Medicine; 1975: 23–35.

    Google Scholar 

  146. Asakura H, Hori M, Umezawa H. Characterization of bleomycin action on DNA.J Antibiot 1975;28: 537–542.

    Google Scholar 

  147. Eckelman WC, Kubota H, Siegel BA. et al. Iodinated bleomycin: an unsatisfactory radiopharmaceutical for tumor localization.J Nucl Med 1976;17: 385–388.

    Google Scholar 

  148. Sinkula AA, Yalkowsky SH. Rationale for design of biologically reversible drug derivatives: prodrugs.J Pharm Sci 1975;64:181–210.

    Google Scholar 

  149. Chen YCJ, Janda K. A new approach toward the inhibition of ribonucleases: a water-stable ribonucleoside-technetium chelate.J Am Chem Soc 1992;114: 1488–1489.

    Google Scholar 

  150. DiZio JP, Anderson CJ, Davison A, Ehrhardt GJ, Carlson KE, Welch MJ, Katzenellenbogen JA. Technetium- and rhenium-labeled progestins: synthesis receptor binding and in vivo distribution of an beta-substituted progestin labeled with technetium-99 and rhenium-186.J Nucl Med 1992; 33: 558–569.

    Google Scholar 

  151. O'Neil JP, Carlson KE, Anderson CJ, et al. Progestin radiopharmaceuticals labeled with Tc and Re: synthesis binding affinity and in vivo distribution of a new progestin N2S2-metal complex.Biocon Chem 1994;5: 182–193.

    Google Scholar 

  152. Chi DY, O'Neil JP, Anderson CJ, Welch MJ, Katzenellenbogen JA. Homodimeric and heterodimeric his (amino thiol) oxometal complex formation and an approach to metal complexes that mimic steroid hormones.J Med Chem 1994;37: 928–937.

    Google Scholar 

  153. Piwnica-Worms D, Chiu ML, Budding M, Kronauge JF, Kramer RA, Croop JM. Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex.Cancer Res 1993;53: 977–984.

    Google Scholar 

  154. Macke HR, Smith-Jones P, Maina T, Stolz B, Albert R, Burns C, Reist H. New octreotide derivatives for in vivo targeting of somatostatin receptor-positive tumors for single photon emission computed tomography (SPECT) and positron emission tomography (PET).Horm Metab Res Suppl 1993;27: 12–17.

    Google Scholar 

  155. Del Rosario RB, Jung Y-W, Baidoo KE, Lever SZ, Wieland DM. Synthesis and in vivo evaluation of a99m/99Tc-DADT-benzovesamicol: a potential marker for cholinergic neurons.Nucl Med Biol 1994;21: 197–204.

    Google Scholar 

  156. Lever SZ, Baidoo KE, Mahmood A, Matsumura K, Scheffel U, Wagner, Jr. HN. Novel technetium ligands with affinity for the muscarinic cholinergic receptor.Nucl Med Biol 1994;21: 157–164.

    Google Scholar 

  157. Top S, Vessieres A, Jaouen G. Synthetic strategy for organometallic complexes of rhenium with exceptionally high-affinity for the aestradiol receptor; their potential uses as imaging and therapeutic agents.J Chem Soc Chem Commun 1994;453–454.

  158. Friedlander G, Kennedy JW, Miller JM.Nuclear and radiochemistry, 2nd edn. New York: John Wiley, 1964.

    Google Scholar 

  159. Boyd RE, Technetium-99m generators — the available options.Int J Appl Radiat Isot 1982;33: 801–809.

    Google Scholar 

  160. Deutsch E, Heineman WR, Zodda J, et al. Preparation of “no-carrier-added” technetium-99m complexes: determination of the total technetium content of generator eluents.Int J Appl Radiat Isot 1982;33: 843–848.

    Google Scholar 

  161. Smith TD, Richards P. A simple kit for the preparation of99mTc-labeled red blood cells.J Nucl Med 1976;17: p126.

    Google Scholar 

  162. Bayne VJ, Forster AM, Tyrrell DA. Use of sodium iodide to overcome the eluate age restriction for Ceretec reconstitution.Nucl Med Commun 1989;10: 29–33.

    Google Scholar 

  163. Stern WD, Transport and diffusion across cell membranes. New York: Academic Press, 1986.

    Google Scholar 

  164. Nowotnik DP, Technetium-based brain perfusion agents. In: Nunn A, ed.Radiopharmaceuticals: chemistry and pharmacology. New York: Marcel Dekker, 1992: 37–95.

    Google Scholar 

  165. Eckelman WC, et al. Receptor binding radiotracers: a class of potential radiopharmaceuticals.J Nucl Med 1979;20: 350–357.

    Google Scholar 

  166. Eckelman WC, In: Eckelman WC, ed., Receptor binding radiotracers, vol 1. Boca Raton FL: CRC Press;1982: 69–91.

    Google Scholar 

  167. Eckelman WC, Radiopharmaceuticals and brain pathology studied with PET and SPECT. In: Diksic M, Reba RC, eds.The testing of putative receptor binding radiotracers in vivo. Boca Raton, FL: CRC Press; 1990: 41–68.

    Google Scholar 

  168. Katzenellenbogen J, The development of gamma-emitting hormone analogs as imaging agents for receptor-positive tumors. In: Murphy GP, Sandberg AA, Karr JP, eds.The pros tatic cell: structure and function, Part B. New York: Alan R Liss;1981: 313–327.

    Google Scholar 

  169. Katzenellenbogen JA, Heiman DF, Carlson KE, Lloyd JE. In vitro and in vivo steroid receptor assays in the design of estrogen radiopharmaceuticals. In: Eckelman W ed.Receptor binding radiotracers. Boca Raton FL: CRC Press;1982: 93–126.

    Google Scholar 

  170. Goodenough DJ, Atkins FB. Radiolabeled monoclonal antibodies for imaging and therapy. In: Srivastava S, ed.Theoretical limitations of tumor imaging. New York: Plenum;1988: 495–512.

    Google Scholar 

  171. Eckelman WC, Gibson RE. The design of site directed radiopharmaceuticals for use in drug discovery. In: Burns H, et al., eds.Nuclear imaging in drug discovery, development and approval. Boston: Birkhauser;1992: 113–134.

    Google Scholar 

  172. Eckelman WC, The application of receptor theory to receptor-binding and enzyme-binding oncologic radiopharmaceuticals.Nucl Med Biol 1994;21: 759–770.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eckelman, W.C. Radiolabeling with technetium-99m to study high-capacity and low-capacity biochemical systems. Eur J Nucl Med 22, 249–263 (1995). https://doi.org/10.1007/BF01081522

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01081522

Key words

Navigation