Quantitative Pharmacokinetics of Radiolabeled Monoclonal Antibodies for Imaging and Therapy in Patients

  • Gerald L. DeNardo
  • Sally J. DeNardo
  • Daniel J. Macey
  • Stanley L. Mills
Part of the NATO ASI Series book series (NSSA, volume 152)


Antibodies can be used to carry radionuclides to tumors for in vivo diagnosis and treatment. Monoclonal antibody reagents have virtually replaced the heterosera of earlier days. When suitably radiolabeled, these antibodies provide potential for imaging and treatment of cancer. The potential of radioimmunoimaging and radioimmunotherapy of cancer based upon monoclonal antibodies has excited the scientific community. These developments provide a unique opportunity for radionuclide imaging based on the specificity of monoclonal antibodies and therapy based on treatment planning techniques analogous to those used in external beam and radionuclide sealed source radiation therapy. Our goal has been to develop a comprehensive treatment planning system for clinical cancer therapy with radiolabeled monoclonal antibodies against cancer-associated antigens. We expect the system to provide estimates of the radiation dose distributions associated with various choices of radionuclide and targeting molecule. These approaches are now feasible because of advances in quantitative radionuclide imaging. Tracer techniques can now be implemented by advanced equipment for quantitative radionuclide imaging and strengthened by dynamic modeling of the physiological parameters which govern radionuclide distribution, and hence radiation dose distribution (1). We believe that quantitative radionuclide imaging is necessary to efficiently and accurately make decisions that can influence the efficacy of radioimmunoimaging and radioimmunotherapy.


Radiation Dosimetry Scatter Fraction Scintillation Camera Pharmacokinetic Information Septal Penetration 
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  1. 1.
    G. L. DeNardo, A. Raventos, H. H. Hines, P. O. Scheibe, D. J. Macey, M. T. Hayes and S. J. DeNardo, Requirements for a treatment planning system for radioimmunotherapy, Internatl. J. Rad. Onc. Biol. Phys. 11:335–345 (1985).CrossRefGoogle Scholar
  2. 2.
    J. A. Carrasquillo, K. A. Krohn, P. Beaumier, R. W. McGuffin, J. P. Brown, K. E. Hellstrom, I. Hellstrom, S. M. Larson, Diagnosis of and therapy for solid tumors with radiolabeled antibodies and immune fragments, Cancer Treat. Repts. 68:317–328 (1984).Google Scholar
  3. 3.
    J-F. Chatal, J-C. Saccavini, P. Fumoleau, J-Y. Douillard, C. Curtet, M. Kremer, B. Le Mevel, H. Koprowski, Immunoscintigraphy of colon carcinoma, J. Nuc. Med. 25:307–314 (1984).Google Scholar
  4. 4.
    F. H. DeLand, D. M. Goldenberg, In vivo cancer diagnosis by radioimmunodetection, in: Radioimmunoimaging and Radioimmunotherapy, S.W. Burchiel and B.A. Rhodes, eds, Elsevier, New York (1983).Google Scholar
  5. 5.
    G. L. DeNardo, S. J. DeNardo, D. J. Macey, Cancer treatment with radioactive labeled antibodies, in: Nuclear Medicine in Clinical Oncology, C. Winkler, ed., Springer-Verlag, Berlin, Heidelberg (1986).Google Scholar
  6. 6.
    A. A. Epenetos, Clinical results with regional antibodyguided irradiation, Cancer Drug Delivery 2:233 (1985).Google Scholar
  7. 7.
    A. A. Epenetos, S. Mather, M. Granowska, C. C. Nimmon, L. R. Hawkins, K. E. Britton, J. Shepherd, J. Taylor-Papadiminitriou, H. Durbin, J. S. Malpas, W. F. Bodmer, Targeting of Iodine-123 labeled tumor- associated monoclonal antibodies to ovarian, breast and gastrointestinal tumors, Lancet 2:999–1004 (1982).PubMedCrossRefGoogle Scholar
  8. 8.
    A. L. Epstein, A. M. Zimmer, S. M. Spies, S. Mills, G. DeNardo, S. DeNardo, Radioimmunodetection of human B cell lymphomas with a radiolabeled tumor-specific monoclonal antibody (Lym-1), in: Malignant Lymphomas and Hodgkin’s Disease: Experimental and Therapeutic Advances, F. Cavalli, G. Bonadonna, M. Rozencweig, eds., Martinus Nijhoff Publishing, Boston (1985).Google Scholar
  9. 9.
    D. M. Goldenberg, F. DeLand, E. Kim, S. Bennett, F. J. Primus, J. R. van Nagell, N. Estes, P. DeSimone, P. Rayburn, Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning, New Eng. J. Med. 298: 1384–1388 (1978).PubMedCrossRefGoogle Scholar
  10. 10.
    S. E. Halpern, R. O. Dillman, K. F. Witztum, J. F. Shega, P. L. Hagan, W. M. Burrows, J. B. Dillman, M. L. Clutter, R. E. Sobol, J. M. Frincke, R. M. Bartholomew, G. S. David, D. J. Carlo, Radioimmunodetection of melanoma utilizing In-111 96.5 monoclonal antibody: A preliminary report, Radiology 155:493–499 (1985).PubMedGoogle Scholar
  11. 11.
    J-P. Mach, J-F. Chatal, J-D. Lumbroso, F. Buchegger, M. Forni, J. Ritschard, C. Berche, J-Y. Douillard, S. Carrel: Tumor localization in patients by radiolabeled antibodies against colon carcinoma, Cancer Res. 43:5593–5600 (1983).PubMedGoogle Scholar
  12. 12.
    J. L. Murray, M. G. Rosenblum, R. E. Sobol, R. M. Bartholomew, C. E. Plager, T. P. Haynie, M. F. Jahns, J. H. Glenn, L. Lamki, R. S. Benjamin, N. Papadoupoulos, A. W. Boddie, J. M Frincke, G. S. David, D. J. Carlo, E. M. Hersh, Radioimmunoimaging in malignant melanoma with In-labeled monoclonal antibody 96.5, Cancer Res. 45:2376–2381 (1985).PubMedGoogle Scholar
  13. 13.
    L. F. O’Grady, G. L. DeNardo, S. J. DeNardo, Radiolabeled monoclonal antibodies for the detection of cancer, Am. J. Physiologic Imaging 1:44–53 (1986).Google Scholar
  14. 14.
    S. E. Order, Monoclonal antibodies: Potential role in radiation therapy and oncology, Internatl. J. Rad. Onc. Biol. Phys. 8:1193–1201 (1982).CrossRefGoogle Scholar
  15. 15.
    M. G. Rosenblum, J. L. Murray, T. P. Haynie, H. J. Glenn, M. F. Jahns, R. S. Benjamin, J. M. Frincke, D. J. Carlo, E. M. Hersh, Pharmacokinetics of 111-In labeled anti-P97 monoclonal antibody in patients with metastatic malignant melanoma, Cancer Res. 45:2382–2386 (1985).PubMedGoogle Scholar
  16. 16.
    G. L. DeNardo, S. J. DeNardo, J-S. Peng, L. F. O’Grady, S. L. Mills, A. L. Epstein, R. D. Cardiff, Evidence of a saturable hepatic receptor for mouse monoclonal antibodies, J. Nuc. Med. 26:67 (1985).Google Scholar
  17. 17.
    S. J. DeNardo, G. L. DeNardo, L. F. O’Grady, J-S. Peng, D. J. Macey, S. L. Mills, R. D. Cardiff, A. L. Epstein, Human Kinetic distribution of I-123 intact antibody, J. Nuc. Med. 26:112 (1985).Google Scholar
  18. 18.
    K. Koizumi, G. L. DeNardo, S. J. DeNardo, J-S. Peng, D. J. Macey, K. Hisada, N. Tonami, Multicompartmental analysis of the kinetics of monoclonal antibody in cancer patients, J. Nuc. Med. 26:91 (1985).Google Scholar
  19. 19.
    S. J. DeNardo, G. L. DeNardo, J-S. Peng, D. Colcher, Monoclonal antibody radiopharmaceuticals for cancer radioimmunotherapy, in: Radioimmunoimaging and Radioimmunotherapy, S. Burchiel, B. Rhodes, eds., Elsevier, New York (1983).Google Scholar
  20. 20.
    D. J. Macey, R. Marshall, The lungs, in: Computed Emission Tomography, P. J. Ell and B. L. Holman, eds., Oxford University Press, New York, Toronto, pp. 495–520, 1982Google Scholar
  21. 21.
    A. L. Epstein, R. J. Marder, J. N. Winter, E. Stathopoulos, F-M. Chen, J. W. Parker, C. R. Taylor, Two new monoclonal antibodies, Lym-1 and Lym-2, reactive with human B lymphocytes and derived tumors with immunodiagnostic and immunotherapeutic potential, Cancer Res. In press.Google Scholar
  22. 22.
    D. J. Macey, R. Marshall, Absolute quantitation of radiotracer up-take in the lungs using a gamma camera, J. Nuc. Med. 23:731–734 (1982).Google Scholar
  23. 23.
    D. J. Macey, G. L. DeNardo, S. J. DeNardo, H. H. Hines, Comparison of low- and medium-energy collimators for SPECT imaging with Iodine-123 labeled antibodies, J. Nuc. Med. 27:1467–1474 (1986).Google Scholar
  24. 24.
    F. B. Atkins, R. N. Beck, P. B. Hoffer, D. Palmer, Dependence of optimum baseline setting on scatter fraction and detector response function in medical radionuclide imaging, IAEA, Vienna (1977).Google Scholar
  25. 25.
    J. W. Beck, R. J. Jaszczak, R. E. Coleman, C. F. Starmer, L. W. Nolte, Analysis of SPECT including scatter and attenuation using sophisticated Monte Carlo modeling methods, IEEE Trans. Nuc. Sci. 506–511 (1982).Google Scholar
  26. 26.
    T. F. Budinger, S. E. Derenzo, W. L. Greenberg, G. T. Gullberg, R. H. Huesman, Quantitative potentials of dynamic emission computed tomography, J. Nuc. Med. 19:309–315 (1978).Google Scholar
  27. 27.
    T. F. Budinger, G. T. Gullberg, Transverse section reconstruction of gamma-ray emitting radionuclides in patients, in: Reconstruction Tomography in Diagnostic Radiology and Nuclear Medicine, M. M Ter-Pogossian, M. E. Phelps, G. L. Brownell et al., eds., University Park Pres, Baltimore (1977).Google Scholar
  28. 28.
    R. J. Jaszczak, L. T. Chang, N. A. Stein, F. E. Moore, Whole body single-photon emission computed tomography using dual, large-field-of-view scintillation cameras, Phys. Med. Biol. 24:1123–1143 (1979).PubMedCrossRefGoogle Scholar
  29. 29.
    R. J. Jaszczak, R. E. Coleman, F. R. Whitehead, Physical factors affecting quantitative measurements using camera based SPECT, IEEE Trans. Nuc. Sci. 28:69–80 (1981).CrossRefGoogle Scholar
  30. 30.
    J. W. Keyes, Perspectives on tomography, J. Nuc. Med. 23:633–640 (1982).Google Scholar
  31. 31.
    G. Muehllehner, J. G. Colsher, E. W. Stoub, Correction for field non-uniformity in scintillation camera through removal of spatial distortion, J. Nuc. Med. 21:771–776 (1980).Google Scholar
  32. 32.
    M. E. Phelps, Emission computed tomography, Seminars in Nuc. Med. 7:337–365 (1977).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Gerald L. DeNardo
    • 1
    • 2
    • 3
  • Sally J. DeNardo
    • 1
    • 2
    • 3
  • Daniel J. Macey
    • 1
    • 2
    • 3
  • Stanley L. Mills
    • 1
    • 2
    • 3
  1. 1.Department of RadiologyUniversity of CaliforniaDavisUSA
  2. 2.Department of Internal MedicineUniversity of CaliforniaDavisUSA
  3. 3.Medical CenterSacramentoUSA

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