Quality Assurance of Radiolabeled Proteins, Peptides and Antisense Oligonucleotides

  • Mrinal K. Dewanjee


Radiopharmaceuticals (RP) labeled with nonmetallic (I–123, C-11, F-18) and metallic radionuclides (Tc-99m, Ga-67, In-111) are used for diagnosis and therapy; they could be classified as blood flow markers, metabolic substrates, receptor ligands, peptide/proteins and antisense oligonucleotide analogs (F-18, 1–123, In-111, Tc-99m). The oligopeptide/nucleotide based tracers, are designed to adhere as “molecular velcro” to target molecules in diseased cells for early, high-contrast imaging. For safety, efficacy and further improvement of the tests using these tracers, quality assurance (QA) of tracers (chemical, radionuclidiC., radiochemical impurities, enantiomers, immunoreactivity, sterility, apyrogenicity, cell-viability) is required. These tests are more critical for the RP under clinical investigations. FDA allows a maximum permissible limit of 10% of the injected radionuclide as impurity. Quality assurance of RP is carried out by thin-layer, size-exclusion/ion-exchange (high pressure liquid transport) chromatography and gel electrophoresis. For therapeutic RP labeled with 1–131 (β, γ), Re-186 (β, γ), Re-188 (β), Y-90 (β), At-211(α) and Bi-212 (α), etc., the level of chemical alterations/degradations, directly by energetic particles or indirectly by free-radicals, is higher for the α-, β- than γ-emitting RP and chemical alterations are time-dependent processes. Considering the adverse reactions (marrow-suppression), unnecessary radiation due to unbound tracers and impurities, QA of RP should be performed and impurities eliminated before RP administration.


Antisense Oligonucleotide Antisense Probe Anti Sense Oligonucleotide Anti Sense Anti Sense Probe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M.K. Dewanjee, M. Tago, M. Josa, V. Fuster and M.P. Kaye Quantification of platelet retention in aortocoronary femoral vein bypass graft in dogs treated with dipyridamole and aspirin. Circulation 69:350–356 (1984).PubMedCrossRefGoogle Scholar
  2. 2.
    M.K. Dewanjee, V.F. Trastek, M. Tago and M.P. Kaye, Radioisotopic techniques for noninvasive detection of platelet deposition in bovine-tissue mitral valve prostheses and in vitro quantification of visceral microembolism in dogs. Invest Radiol 19:535–542 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    M.K. Dewanjee, E. Solis, S.T. Mackey, S. Socher, S. Chowdhury, F.P. Wu, and M.P. Kaye, Quantification of deposition of neutrophilic granulocytes on vascular grafts in dogs with In-111-labeled granulocytes. Mayo Clinic Proc 60:173–179 (1985).CrossRefGoogle Scholar
  4. 4.
    M.K. Dewanjee. Cardiac and vascular imaging with labeled platelets and leukocytes. Sem Nucl Med XIV: 154–187 (1984).Google Scholar
  5. 5.
    M.K. Dewanjee. Methods of assessments of thrombosis in vivo. Blood in contact with natural and artificial surfaces. Vol. 516, Theme 4, Part one. E.F. Leonard, L. Vroman, V.T. Turitto, eds., New York Academy of Science, New York, N.Y., 541–571 (1987).Google Scholar
  6. 6.
    M.K. Dewanjee. Chemistry of 99mTc-labeled radiopharmaceuticals. Sem Nucl Med XX: 5–27 (1990).Google Scholar
  7. 7.
    A.N. Serafini. From monoclonal antibodies to peptides and molecular recognition units: an overview. J Nucl Med 34: 533–536 (1993).PubMedGoogle Scholar
  8. 7a.
    J. Scholm. Innovations in monoclonal antibody tumor targeting. Diagnostic and therapeutic implications. JAMA 261: 744–746 (1989).CrossRefGoogle Scholar
  9. 7b.
    D.M. Goldenberg. Future role of radiolabeled monoclonal antibodies in oncological diagnosis and therapy. Semin Nucl Med 19: 332–339 (1989).PubMedCrossRefGoogle Scholar
  10. 7c.
    C.E. Neal, L.C. Swenson and J. Fanning, et al. Monoclonal antibodies in ovarian and prostate cancer. Sem Nucl Med XXIII: 114–126 (1993).Google Scholar
  11. 7d.
    D.A. Podoloff, Y.Z. Patt and S.A. Curley, et al. Imaging of colorectal carcinoma with Tc-99m radiolabeled Fab’ fragments. Sem Nucl Med XXIII: 89–98 (1993).Google Scholar
  12. 7e.
    M.A. Bakir, S.A. Eccles, J.W. Babich, N. Aftab, J.M. Styles, C.J. Dean, and R.J. Ott. c-erbB2 protein overexpression in breast cancer as a target for PET using iodine-124 labeled monoclonal antibodies. J Nucl Med. 33:2154–2160 (1992).PubMedGoogle Scholar
  13. 8.
    A.E. Martell and R.M. Smith. Critical Stability Constants. Plenum Press, New York, (1974).Google Scholar
  14. 9.
    M. Sundberg, C. Meares, D. Goodwin and C. Diamanti. Selective binding of metal ions to macromolecules using bifunctional analogs of EDTA. J Med Chem 17:1304–1307 (1974).PubMedCrossRefGoogle Scholar
  15. 10.
    M.W. Brechbiel, O.A. Gansow, R.W. Atcher, J. Scholm, J. Esteban, D.E. Simpson D. Colcher. Synthesis of 1-(p-isothiocyanatobenzyl) derivatives of DTPA and EDTA. Antibody labeling and tumor imaging studies. Inorg Chem 25:2772–2781 (1981).CrossRefGoogle Scholar
  16. 11.
    O. Renn and C.F. Meares. Large scale synthesis of the bifunctional chelating agent 2-(p-nitrobenzyl)-1, 4, 7, 10-tetraazacyclododecane-N, N′, N″, N″′-tetraaceticacidand the determination of its enantiomeric purity by chiral chromatography. Bioconjug Chem 3:563–569 (1992).PubMedCrossRefGoogle Scholar
  17. 12.
    R. Subramanian, J. Colony, S. Shaban, H. Sidrak, M.V. Haspel, N. Pomato and M.G. Hanna. New chelating agent for attaching indium-111 to monoclonal antibodies: in vitro and in vivo evaluation. Bioconjugate Chem 3:248–255 (1992).CrossRefGoogle Scholar
  18. 13.
    G.E. Krejcarek and K.L. Tucker. Covalent attachment of chelating groups to macromolecules. Biochem Biophys Res Commun 77:581–585 (1977).PubMedCrossRefGoogle Scholar
  19. 14.
    D.J. Hnatowich, W.W. Layne and R.L. Childs, et al: Radioactive labeling of antibody: a simple and efficient method. Science 220:613–615 (1983).PubMedCrossRefGoogle Scholar
  20. 15.
    A.R. Fritzberg, P.G. Abrams and P.L. Beaumier et al, Specific and stable labeling of antibodies with technetium-99m using a diamide dithiolate (N2S2) chelating agent. Proc Natl Acad Sci 85:4025–4029 (1988).PubMedCrossRefGoogle Scholar
  21. 16.
    W.C. Eckelman and C.H. Paik. Labeling antibodies with metals using bifunctional chelates. Chapter 6, In Antibodies in Radiodiagnosis and Therapy, Ed. M. Zalutsky; CRC Press, Boca Raton, 1989, pp 103–128.Google Scholar
  22. 17.
    S. Miller, A.M. Lesk, J. Janin and C. Chothia. The accessible area and stability of oligomeric proteins. Nature 328:834–837 (1987).PubMedCrossRefGoogle Scholar
  23. 18.
    T.E. Creighton. The folded conformations of globular proteins, Chapter 6 and Degradation, Chapter 10, In Proteins: Structures and Molecular Properties, Freeman and Co., New York, 201–260 and 463–474.Google Scholar
  24. 19.
    D. Staunton, A.E. Jones and A.R. Rees. Creation of a metal-binding site within the antibody combining site. In Miami Winter Symposium on Biotechnology (1993), Advances in Gene Technology: Protein Engineering and Beyond, p 91.Google Scholar
  25. 20.
    M.E. Izard, G.R. Boniface and K.L. Hardiman et al, An improved method for labeling monoclonal antibodies with samarium-153: use of the bifunctional chelate 2(p-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid. Bioconjug Chem 3:346–350 (1992).PubMedCrossRefGoogle Scholar
  26. 21.
    E. John, M.L. Thakur and J. DeFulvio et al, Rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: preparation and evaluation. J Nucl Med 34:260–267 (1993).PubMedGoogle Scholar
  27. 21a.
    21a.S. Garg, P.K. Garg and M.R. Zalutsky. Labeling monoclonal antibodies with At-211 usng N-succinimidyl 5-[At-211] astato-3-pyridinecarboxylate (SAPC). J Nucl Med 34:99P, (1993) (Abstract).Google Scholar
  28. 22.
    R.B. Merrifield. Solid phase peptide synthesis. I. Synthesis of a tetrapeptide. J Am Chem Soc 15:2149–2154 (1963).CrossRefGoogle Scholar
  29. 23.
    J.M. Stewart and J.D. Young. Solid phase peptide synthesis. W.H.Freeman & Company, San Francisco, CA, (1969).Google Scholar
  30. 24.
    G. Kohler and C. Milstein, Continuous cultures of fused cells secreting antibodies of predefined specificity. Nature 256:495–497 (1975).PubMedCrossRefGoogle Scholar
  31. 24a.
    S.L. Morrison. Genetically engineered chimeric antibodies. Hosp Pract 15:65–79(1989).Google Scholar
  32. 25.
    S. Dubel, F. Breitling and P. Fuchs et al, A family of vectors for surface display and production of antibodies. Gene 128:97–101 (1993).PubMedCrossRefGoogle Scholar
  33. 26.
    M. Iqbal, P. Balaram and H.J. Showell et al, Conformationally constrained chemotactic peptide analogs of high biological activity. FEBS 165:171–174 (1984).CrossRefGoogle Scholar
  34. 27.
    M.C. Pike and R. Snyderman, Leukocyte chemoattractant receptors. Methods Enzymol 162:236–245 (1988).PubMedCrossRefGoogle Scholar
  35. 27a.
    27a.R.P. McEver and M.N. Martin, A monoclonal antibody to membrane glycoprotein binds to activated platelets. J Biol Chem 259:9799–9804 (1984).PubMedGoogle Scholar
  36. 27b.
    D.D. Miller, A.J. Boulet, F.O. Tio et al, In vivo Tc-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty. Circulation 83:224–236 (1991).PubMedCrossRefGoogle Scholar
  37. 27c.
    R. Taub, R.J. Goulda and V.M. Gorsky et al, A monoclonal antibody against the platelet fibrinogen receptor contains a sequence that mimics a receptor recognition domain in fibrinogen. J Biol Chem 64:259–265 (1989).Google Scholar
  38. 27d.
    S.F. Rosebrough, J.G. McAfee and Z.D. Grossman et al, Immunoreactivity of In-111 and 1–131 fibrin-specific monoclonal antibody used for thrombus imaging. J Immunol Methods 116:123–129 (1989).PubMedCrossRefGoogle Scholar
  39. 27e.
    E. Haber. Antibodies in cardiovascular diagnosis and therapy. Hosp Pract 21:147–172, (1986).Google Scholar
  40. 27f.
    P. Manspeaker, H.F. Weisman and T.F. Schaible, Cardiovascular applications: current applications of immunoscintigraphy in the detection of myocardial necrosis using antimyosin (R11D10) and deep vein thrombosis using antifibrin (T2G1S). Sem Nucl Med XXIII: 133–147 (1993).Google Scholar
  41. 27g.
    B.A. Khaw, T. Yasuda and H.K. Gold et al, Acute myocardial infarct imaging with In-111 labeled monoclonal antimyosin Fab. J Nucl Med 28:1671–1678 (1987).PubMedGoogle Scholar
  42. 28.
    R.D. Mayforth and J. Quintans, Designer and catalytic antibodies. N Engl J Med 323: 173–178 (1990).PubMedCrossRefGoogle Scholar
  43. 29.
    M. Paulsson. Basement membrane proteins: structure, assembly and cellular interactions. Critical Reviews in Biochemistry and Molecular Biology, 27(l/2):93–127 (1992).PubMedGoogle Scholar
  44. 30.
    S. Vallabhajosula, kS.K.M. Ali and S.J. Goldsmith et al, Evaluation of Tc-99m labeled peptides for imaging atherosclerotic lesions in vivo. J Nucl Med 34:66P (1993). (Abstract).Google Scholar
  45. 31.
    A.J. Fischman, M.C. Pike and D. Kroon et al, Imaging of focal sites of bacterial infection in rats with In-111 labeled chemotactic peptide analogs. J Nucl Med 32:483–491 (1991).PubMedGoogle Scholar
  46. 32.
    A. Fischman, D. Rauh and H.F. Solomon et al, Imaging of focal sites of inflammation in nonhuman primates with a Tc-99m labelled chemotactic peptide. J Nucl Med 34:104P and 174P (1993). (Abstract).Google Scholar
  47. 33.
    M.J. Abrams, M. Juweid and C.I. TenKate et al, Tc-99m human polyclonal IgG radiolabeled via the hydrazinonicotinamide derivative for imaging focal sites of infection in rats. J Nucl Med 31:2022–2028 (1990).PubMedGoogle Scholar
  48. 34.
    L.C. Knight. Scintigraphic methods for detecting vascular thrombus. J Nucl Med 34:554–561 (1993).PubMedGoogle Scholar
  49. 35.
    L.C. Knight, A.H. Maurer, J. Romano and S. Buczala, Preliminary evaluation of labeled disintegrins (snake venom peptides) for thrombus imaging. J Nucl Med 34:66P (1993). (Abstract).Google Scholar
  50. 36.
    E.P. Krenning, W.H. Bakker and P.P.M. Kooij et al, Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]-octreotide in man: metabolism, dosimetry, and comparison with [123I-Tyr3-octreotide. J Nucl Med 33:652–658 (1993).Google Scholar
  51. 36a.
    36a.S.W.J. Lamberts, E.P. Krenning and J.C. Reubi, The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocrine Rev 12:450–482 (1991).CrossRefGoogle Scholar
  52. 37.
    A.N. Serafini, R. Vargas-Cuba, P. Benedetto, A. Legaspi, L. Feunn, D. Robinson, B. Ardalan, M.K. Dewanjee, B. Sevin, H. Averette and G.N. Sfakianakis, Clinical experience in utilizing radiolabeled monoclonal antibodies. Antibody, Immunoconjugates and Radiopharmaceuticals. 4(l):77–83 (1991).Google Scholar
  53. 38.
    G. Carpenter and S. Cohen, 125I-labeled human epidermal growth factor: binding, internalization and degradation in human fibroblasts, J Cell Biol 71:159 (1976).PubMedCrossRefGoogle Scholar
  54. 39.
    P.A. Charlwood, E. Regoeczi and M.W.C. Hatton, Hepatic uptake and degradation of trace doses of asialofetuin and asialoorosomucoid in the intact rat. Biochim Biophys Acta 585, 61 (1979).PubMedCrossRefGoogle Scholar
  55. 40.
    C.F. Fox, P.S. Linsley and M. Wrann, Receptor remodeling and regulation in the action of epidermal growth factor, Fed Proc 41:2988 (1982).PubMedGoogle Scholar
  56. 41.
    S.L. Loke, C.A. Stein, X.H. Zhang, K. Mori, M. Nakanishi, C. Subasinghe, J.S. Cohen and L.M. Neckers, Characterization of oligonucleotide transport into living cells. Proc Natl Acad Sci 86:3473–3478 (1989).CrossRefGoogle Scholar
  57. 42.
    D.C. Anderson, R. Manger, J. Schroder et al, Enhanced in vitro tumor cell retention and internalization of antibody derivatized with synthetic peptides. Bioconjug Chem 4:10–18(1993).Google Scholar
  58. 43.
    S. Kinuya, J.M. Jeong, T. Saga, L. Camera et al, Effect of degree of conjugation per MOAB on metabolism and clearance of its In-111 chelate in mice. J Nucl Med 34:58 (1993).Google Scholar
  59. 44.
    J.R. Duncan and M.J. Welch. Receptor targeted radiolabeled polypeptides: intracellular metabolism. J Nucl Med 34:59 (1993). (Abstract).Google Scholar
  60. 45.
    D.J. Hnatowich, F. Virzi, P. Winnard et al, Can a cysteine-challenge assay predict the in vivo stability and biodistribution of Tc-99m labeled to antibodies? J Nucl Med 34:59 (1993).Google Scholar
  61. 46.
    M.K. Dewanjee. Radioiodinated peptides and growth factors and their applications. Chapter 14, In Radioiodination: Theory, and Biomedical Applications. Kluwer Academic Publishers, Boston p523–531 (1992). ibid, Chapter 17 Preparation and purification of substrates and proteins before and after radioiodination, p551–580, ibid, Chapter 18, Quality control of radioiodinated products, p581–596, autoradiography p586–593, ibid, Chapter 19, Specific activity and radiation damage in tracers during storage, p597–609, Chapter 12, Radioiodinated antisense probes in gene activation and proliferation, p484–491.CrossRefGoogle Scholar
  62. 47.
    R. Ralston and J.M. Bishop, The protein products of the oncogene myC., myb and adenovirus Ela are structurally related. Nature 306:803–806 (1983).PubMedCrossRefGoogle Scholar
  63. 47a.
    J.M. Bishop, Molecular themes in oncogenesis. Cell 64:235–248 (1991).PubMedCrossRefGoogle Scholar
  64. 47b.
    M.E. Harper, L.M. Marselle, R.C. Gallo and F. Wong-Staal, Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci USA 83:772–776 (1986).PubMedCrossRefGoogle Scholar
  65. 48.
    J.B. Lum, Visualization of mRNA transcription of specific genes in human cells and tissues using in situ hybridization. BioTechniques 4:32–39 (1986).Google Scholar
  66. 49.
    S.A. Narang, T.M. Jacobs, H.G. Khorana, Studies on polynucleotides. LXIII. Deoxyribopoly-nucleotides containing repeating trinucleotide sequences. The polymerization of protected deoxyribonucleotides. J Amer Chem Soc; 89:2158–2177 (1967).CrossRefGoogle Scholar
  67. 50.
    M.D. Matteucci and M.H. Caruthers, Synthesis of deoxyoligo-nucleotides on a polymer support. J Amer Chem Soc 103:3185–3191 (1981).CrossRefGoogle Scholar
  68. 50a.
    B.A. Connolly, The synthesis of oligonucleotides containing a primary amino group at the 5’-terminus. Nucl Acid Res 15(7): 3131–3139 (1987); Aminolink-2, User Bull. No. 49, Applied Biosystems, Inc.CrossRefGoogle Scholar
  69. 50b.
    Sulfurization with TETD: phosphorothioate oligonucleotide synthesis via phosphoramidite chemistry. Applied Biosystems Inc. User Bulletin, No. 58, Feb. (1991).Google Scholar
  70. 51.
    S.T. Crooke, Therapeutic approaches of oligonucleotides. Ann Rev Pharmacol Toxicol 32:329–376 (1992).CrossRefGoogle Scholar
  71. 52.
    S.T. Crooke, and B. Lebleu, Antisense research and applications. CRC Press, Boca Raton, FL, (1993).Google Scholar
  72. 53.
    J.P. Leonetti, P. Machy, G. Degols, B. Lebleu and L. Leserman, Antibody-targeted liposomes containing oligodeoxyribonucleotides complementary to viral DNA selectively inhibit viral replication. Proc Natl Acad Sci USA 87:2448 (1990).PubMedCrossRefGoogle Scholar
  73. 54.
    S. Akhtar, Y. Shoji and R.L. Juliano, Pharmaceutical aspects of the biological stability and membrane transport characteristics of antisense oligonucleotides. Gene Regulation: Biology of Antisense RNA and DNA. Eds. Erickson and Izant JG. Raven Press, New York pl33–146 (1992).Google Scholar
  74. 55.
    A.M. Pyle, J.A. McSwiggen and C.R. Cech, Direct measurement of oligonucleotide substrate binding to wild-type and mutant ribozymes from Tetrahymena. Proc Natl Acad Sci. 87:8187 (1990).PubMedCrossRefGoogle Scholar
  75. 56.
    W.F. Lima, B.P. Monia, D.J. Ecker and S.M. Frier, Implication of mRNA structure on antisense oligonucleotide hybridization kinetics. Biochemistry 31:12055 (1992).PubMedCrossRefGoogle Scholar
  76. 57.
    J.D. Puglisi and I. Tinoco, Absorbance melting curves of RNA. Methods Enzymol 180: 304 (1989).PubMedCrossRefGoogle Scholar
  77. 58.
    C. Szczylik, T. Skorski, N.C. Nicolaides, L. Manzella, L. Malaguernera, D. Venturelli A.M. Gewirtz and B. Calabretta, Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligonucleotides. Science 253:562–565 (1991).PubMedCrossRefGoogle Scholar
  78. 59.
    E. Wickstrom, Prospects for antisense nucleic acid therapy of cancer and AIDS. Wiley-Liss Inc., New York p25–33 (1991).Google Scholar
  79. 60.
    E. Wickstrom, Oligonucleotide degradation by nuclease. J Biochem Biophys Methods 13: 97–102 (1986).PubMedCrossRefGoogle Scholar
  80. 61.
    E. Wickstrom, Antisense DNA control of c-myc gene expression, proliferation and differentiation in HL-60 cells. In Antisense RNA and DNA. Ed JAH Murray, Wiley-Liss, p317–334 (1992).Google Scholar
  81. 62.
    R. Watt, L.W. Stanton, K.B. Marcu, R.C. Gallo, C.M. Croce and G. Rovera, Nucleotide sequence of cloned cDNA of human c-myc oncogene. Nature 303:725–728 (1983).PubMedCrossRefGoogle Scholar
  82. 63.
    E.M. Blackwood, R.N. Eisenman, Max: A helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with myc. Science 251:1211–1217 (1991).PubMedCrossRefGoogle Scholar
  83. 64.
    D. Yu, J. Hamada, H. Zhang, G.L. Nicholson and M.C. Hung, Mechanism of c-erb2/neu oncogene-induced metastasis and repression of metastatic properties by adenovirus 5 E1A gene products. Oncogene 7:2263–2270 (1992).PubMedGoogle Scholar
  84. 65.
    M. Park, G.F. Vande Woude, Oncogene: genes associated with neoplastic diseases. In C.R. Scriver, A.L. Beaudet, W.S. Syl and D. Valle, eds. The metabolic basis of inherited disease. New York, McGraw-Hill p251–277 (1989).Google Scholar
  85. 66.
    P.S. Patricia, Invasion and metastasis. Current Opinion in Oncology, 134–141 (1992).Google Scholar
  86. 67.
    M.J. van de Vijer and N.R. Usse, The molecular biology of breast cancer. Biochem Biophys Acta 1072:33–50 (1991).Google Scholar
  87. 68.
    A. Wellstein and M.E. Lippman, Fibroblast growth factors and breast cancer. Chap 18. In Molecular Foundations of Oncology, S. Broder, Williams and Wilkins, eds. p403–418 (1991).Google Scholar
  88. 69.
    M.K. Dewanjee. Treatment of collagenous tissue. US Patent # 4–553974, sole inventor LPC(HOSH).Google Scholar
  89. 70.
    R.Y. Walder and J.A. Walder, Role of RNase H in hybrid-arrested translation by antisense oligonucleotides. Proc Natl Acad Sci 85:5011–5015 (1988).PubMedCrossRefGoogle Scholar
  90. 71.
    M.K. Dewanjee, R. Vargas-Cuba, A.K. Ghafouripour, A. Ganju-Krishan, M. Subramanian, M. Hanna, M. Kapadvanjwala, A.N. Serafini and G.N. Sfakianakis, Kinetics of cellular uptake by intracellular hybridization of c-myc mRNA oncogene with In-111 labeled anti-sense probes in murine leukemic cells (P388s). J Nucl Med 34:224P (1993). (Abstract).Google Scholar
  91. 72.
    M.K. Dewanjee, A.K. Ghafouripour, M. Subramanian, M. Hanna, M. Kapadvanjwala A.N. Serafini, D. Lopez and G.N. Sfakianakis Non-invasive imaging of c-myc oncogene mRNA with radiolabeled anti-sense (RAS) probes in mammary tumor model in mouse. J Nucl Med 34:224P (1993) (Abstract).Google Scholar
  92. 72a.
    M.K. Dewanjee. Radiolabeled antisense probes: diagnosis and therapy. Diagnostic Oncology (In Press, 1993).Google Scholar
  93. 72b.
    M.K. Dewanjee, A.K. Ghafouripour, R.K. Werner, A.N. Serafini and G.N. Sfakianakis Development of sensitive radioiodinated anti-sense oligonucleotide probes by conjugation technique. Bioconjugate Chemistry 2:195–200 (1990).CrossRefGoogle Scholar
  94. 73.
    Y.W. Ebright, Y. Chen, P.S. Pendergrast and R.H. Ebright. Incorporation of an EDTA-metal complex at a rationally selected site within a protein: application to EDTA-iron DNA affinity cleaving with catabolite gene activator protein and Cro. Biochemistry 31:10664–10670 (1992).PubMedCrossRefGoogle Scholar
  95. 74.
    J.M. Kean and P.S. Miller, Detection of psoralen cross-link sites in DNA modified by psoralen-conjugatedoligodeoxyribonucleosidemethylphosphonates. Bioconjug Chem 4:184–187(1993).PubMedCrossRefGoogle Scholar
  96. 75.
    M.K. Dewanjee, S.C. Chowdhury, T. Herold, A.N. Serafini and G.N. Sfakianakis: Endotoxin testing with limulus amoebocyte lysate in a radiopharmaceutical con taining chelated metallic radionuclides and chelated agents. J Nucl Med 31(2):243–245 (1990).PubMedGoogle Scholar
  97. 76.
    S. Hjertén and R. Mosbach, “Molecular sieve” chromatography of proteins on columns of crosslinked Polyacrylamide, Anal Biochem, 3, 109 (1962).PubMedCrossRefGoogle Scholar
  98. 77.
    I. M. Chaiken, M. Wilchek and I. Parikh. International Symposium on Affinity Chromatography and Biological Recognition (1983), Annapolis, Md., Academic Press, Orlando, (1984).Google Scholar
  99. 78.
    O.H. Lowry, N.J. Rosebrough, A.L. Farr and R.J. Randall, Protein measurement with the folin phenol reagent, J Biol Chem, 193, 265 (1951).PubMedGoogle Scholar
  100. 79.
    W.S. Young, In situ hybridization with oligodeoxyribonucleotide probes. Chapter 3, In Situ Hybridization: A Practical Approach. D.G. Wilkinson ed, IRL Press, Oxford, p33–34 (1992).Google Scholar
  101. 80.
    J. Sambrook, E.F. Fritsch and T. Maniatis, Synthetic oligonucleotide probes. Chapter 11, In Molecular Cloning, A Laboratory Manual. Cold Spring Harbor Laboratory Press, New York. Vol 2, p11.3–11.58 (1989).Google Scholar
  102. 81.
    E.M. Southern, Detection of specific sequences among DNA fragments separated by electrophoresis. J Mol Biol 98:503–517 (1975).PubMedCrossRefGoogle Scholar
  103. 82.
    M. Grunstein and D.S. Hogness. Colony hybridization: A method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci 72:3961–3965 (1975).PubMedCrossRefGoogle Scholar
  104. 83.
    W.D. Benton and R.W. Davis, Hybridization in situ of SV40 plaques: detection of recombinant SV40 virus carrying specific sequences of non-viral DNA. Science 196:180–182(1977).Google Scholar
  105. 84.
    A. Chollet and E.H. Kawashima, Biotin-labeled synthetic oligonucleotides: chemical synthesis and uses as hybridization probes. Nucl Acid Res 13(5): 1529–1541 (1985).CrossRefGoogle Scholar
  106. 85.
    S.P. Pulaski and N.T. Hatzenbuhler, Investigations of columns and conditions for the large scale HPLC purification of oligodeoxyribonucleotides. BioChromatography 41–45 (1989).Google Scholar
  107. 86.
    W.J. Warren, G. Vella, Analysis of synthetic oligodeoxynucleotides by capillary gel electrophoresis and anion-exchange HPLC. BioTechniques 14:598–606 (1993).PubMedGoogle Scholar
  108. 87.
    S. Borman, Glycotechnology drugs begin to emerge from the lab. Chem & Eng News 2–36 (1993) (June 28).Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Mrinal K. Dewanjee
    • 1
  1. 1.Department of Radiology, Division of Nuclear MedicineUniversity of Miami School of MedicineMiamiUSA

Personalised recommendations