Volume 3, Issue 3

Original research papers

Radiation in Medicine


M.V. Zhukovsky, Hesham M.H. Zakaly

Pages: 152–158

DOI: 10.21175/RadJ.2018.03.026

Received: 5 JUN 2018, Received revised: 22 NOV 2018, Accepted: 27 NOV 2018, Published online: 28 FEB 2019

The purpose was to assess the behavior of monoclonal antibodies (MAb) and their fragments labeled by 89Zr after injecting them into the human body for the purpose of positron emission tomography (PET), as well as to assess absorbed doses in organs and tissues with maximum radiation exposure. The biokinetic model has been built on the base reference data about the behavior of MAb and their fragments and on the literature data on the excretion of chelate complexes from the human body. The cumulative activity of 89Zr in organs and tissues per Bq of administered activity was calculated. For the most exposed organs, average absorbed doses for organs and tissues were calculated. The organs which had the highest doses, when 89Zr was injected into the human body associated with intact monoclonal antibodies, are the spleen, the liver, and the heart wall. The estimated doses on these organs are 1.69, 1.48 and 1.08 mGy/MBq, respectively. When the injection associated with the fragments of monoclonal antibodies is considered, the most exposed organs are the kidneys with the doses of 0.939 mGy/MBq for F(ab’)) and 0.920 mGy/MBq for F(ab')2.
  1. A. M. Wu, P. D. Senter, “Arming antibodies: prospects and challenges for immunoconjugates,” Nat. Biotechnol., vol. 23, no. 9, pp.1137 – 1146, Sep. 2005.
    DOI: 10.1038/nbt1141
    PMid: 16151407
  2. A. M. Wu, “Engineered antibodies for molecular imaging of cancer”, Methods, vol. 65, no. 1, pp. 139 – 147, Jan. 2014.
    DOI: 10.1016/j.ymeth.2013.09.015
    PMid: 24091005
    PMCid: PMC3947235
  3. T. J. Wadas, E. H. Wong, G. R. Weisman, C. J. Anderson, “Coordinating radiometals of copper, gallium, indium, yttrium, and zirconium for PET and SPECT imaging of disease,” Chem. Rev. vol. 110, no. 5, pp. 2858 – 2902, Apr. 2010.
    DOI: 10.1021/cr900325h
    PMid: 20415480
    PMCid: PMC2874951
  4. Nuclear Decay Data for Dosimetric Calculations, ICRP Publication 107, ICRP, Ottawa, Canada, 2008.
    DOI: 10.1016/j.icrp.2008.10.004
    PMid: 19285593
  5. W. B. Cai et al., “Quantitative PET of EGFR expression in xenograft-bearing mice using Cu-64-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody,” Eur. J. Nucl. Med. Mol. Imaging, vol. 34, no. 6, pp. 850 – 858, Jun. 2007.
    DOI: 10.1007/s00259-006-0361-6
    PMid: 17262214
  6. P. Paudyal et al., “Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with 64Cu-labeled trastuzumab PET,” Cancer. Sci., vol. 101. no. 4, pp. 1045 – 1050, Apr. 2010.
    DOI: 10.1111/j.1349-7006.2010.01480.x
    PMid: 20219072
  7. P. K. E. Borjesson et al., “Performance of Immuno-Positron Emission Tomography with Zirconium-89 Labeled Chimeric Monoclonal Antibody U36 in the Detection of Lymph Node Metastases in Head and Neck Cancer Patients,” Clin. Cancer. Res.,vol. 12, no. 7, pp. 2133 – 2140, Apr. 2006.
    DOI: 10.1158/1078-0432.CCR-05-2137
    PMid: 16609026
  8. I. Verel et al., “High-quality 124I-labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy,” Eur. J. Nucl. Med. Mol. Imaging, vol. 31, no. 12, pp. 1645 – 1652, Dec. 2004.
    DOI: 10.1007/s00259-004-1632-8
    PMid: 15290121
  9. J. P. Holland, M. J. Williamson, J. S. Lewis, “Unconventional Nuclides for Radiopharmaceuticals,” Mol. Imaging, vol. 9, no. 1, pp. 1 – 20, Jan. 2010.
    DOI: 10.2310/7290.2010.00008
    PMid: 20128994
    PMCid: PMC4962336
  10. W. E. Meijs, J. D. M. Herscheid, H. J. Haisma, H. M. Pinedo, “Evaluation of desferal as a bifunctional chelating agent for labeling antibodies with Zr-89,” Appl. Radiat. Isot., vol. 43, no. 12, pp. 1443 – 1447, Dec. 1992.
    DOI: 10.1016/0883-2889(92)90170-J
  11. C. R. Fletcher, “The radiological hazards of zirconium-95 and niobium-95,” Health Phys., vol. 16, no. 2, pp. 209 – 220, Feb. 1969.
    DOI: 10.1097/00004032-196902000-00011<
    PMid: 5772185
  12. S. M. Chiavenna, J. P. Jaworski, A. Vendrell, “State of the art in anti-cancer mAbs,” J. Biomed. Sci., vol. 24, no. 15, pp. 1 – 12, Feb. 2017.
    DOI: 10.1186/s12929-016-0311-y
  13. L. Lindenberg et al., “Dosimetry and first human experience with 89Zr-panitumumab,” Am. J. Nucl. Med. Mol. Imaging, vol. 7, no. 4, pp. 195 – 203, 2017.
    PMid: 28913158
    PMCid: PMC5596322
  14. Radiation Dose to Patients from radiopharmaceuticals: A Compendium of Current Information Related to Frequently Used Substances,ICRP Publication 128, ICRP, Ottawa, Canada, 2015.
    DOI: 10.1177/0146645314558019
    PMid: 26069086
  15. Human Alimentary Tract Model for Radiological Protection, ICRP Publication 100, ICRP, Ottawa, Canada, 2006.
    DOI: 10.1016/j.icrp.2006.03.004
    PMid: 17188183
  16. R. W. Leggett, “The biokinetics of inorganic cobalt in the human body,” Sci. Total Environ., vol. 389, no. 2-3, pp. 259 – 269, Jan. 2008.
    DOI: 10.1016/j.scitotenv.2007.08.054
    PMid: 17920105
  17. R. W. Leggett, “A biokinetic model for zinc for use in radiation protection,” Sci. Total Environ., vol. 420, pp. 1 – 12, Mar. 2012.
    DOI: 10.1016/j.scitotenv.2012.01.013
    PMid: 22326317
  18. W. B. Li, M. Greiter, U. Oeh, C. Hoeschen, “Reliability of a new biokinetic model of zirconium in internal dosimetry: part II, parameter sensitivity analysis,” Health Phys., vol. 101, no. 6. pp. 677 – 692, Dec. 2011.
    DOI: 10.1097/HP.0b013e318226edc0
  19. J. A. Carrasquillo et al., “(124)I-huA33 Antibody PET of Colorectal Cancer,” J. Nucl. Med., vol. 52, no. 8, pp. 1173 – 1180, Jul. 2011.
    DOI: 10.2967/jnumed.110.086165
    PMid: 21764796
    PMCid: PMC3394182
  20. A. L. Klibanov et al., “Blood Clearance of Radiolabeled Antibody: Enhancement by Lactosamination and Treatment with Biotin-Avidin or Anti-Mouse IgG Antibodies” J. Nucl. Med., vol. 29, no. 12, pp. 1951 – 1956, Dec. 1988.
    PMid: 2848113
  21. D. R. Mould, K. R. D. Sweeney, “The pharmacokinetics and pharmacodynamics of monoclonal antibodies – mechanistic modeling applied to drug development,” Curr. Opin. Drug Discov. Devel, vol. 10, no. 1, pp. 84 – 96, Jan. 2007.
    PMid: 17265746
  22. E. C. Dijkers et al., “Biodistribution of 89Zr-trastuzumab and PET Imaging of HER2-Positive Lesions in Patients With Metastatic Breast cancer,” Clin. Pharmacol. Ther., vol. 87, no. 5, pp. 586 – 592, May 2010.
    DOI: 10.1038/clpt.2010.12
    PMid: 20357763
  23. I. Buchmann et al., “A comparison of the biodistribution and biokinetics of 99mTc-anti-CD66 mAb BW 250/183 and 99mTc-anti-CD45 mAb YTH 24.5 with regard to suitability for myeloablative radioimmunotherapy,” Eur. J. Nucl. Med. Mol. Imaging, vol. 30, no. 5, pp. 667 – 673, May 2003.
    DOI: 10.1007/s00259-002-1106-9
    PMid: 12599012
  24. C.-A. Vogel et al., “Direct comparison of a radioiodinated intact chimeric anti-CEA MAb with its F(ab`)2, fragment in nude mice bearing different human colon cancer xenografts,” Br. J. Cancer, vol. 68, no. 4, pp. 684 – 690, Oct. 1993.
    DOI: 10.1038/bjc.1993.410
    PMid: 8398694
    PMCid: PMC1968595
  25. T. Olafsen et al., “Optimizing Radiolabeled Engineered Anti-p185HER2 Antibody Fragments for in vivo Imaging,” Cancer Res., vol. 65, no. 13, pp. 5907 – 5916, 2005.
    DOI: 10.1158/0008-5472.CAN-04-4472
    PMid: 15994969
    PMCid: PMC4161125
  26. J. W. Stathler et al., “The Retention of 14C-DTPA in Human Volunteers after Inhalation or Intravenous Injection,” Health Phys., vol. 44, no. 1. pp. 45 – 52, Jan. 1983.
    DOI: 10.1097/00004032-198301000-00006
  27. V. F. Khokhryakov et al., “Successful DTPA Therapy in the Case of 239Pu Penetration via Injured Skin Exposed to Nitric Acid,” Radiat. Prot. Dosim., vol, 105, no. 1-4, pp. 499 – 502, Jul. 2003.
    DOI: 10.1093/oxfordjournals.rpd.a006291
    PMid: 14527017
  28. WinAct version 1.0, ORNL, Oak Ridge (TN), USA, 2002.
    Retrieved from: https://www.ornl.gov/crpk/software;
    Retrieved on: May 18, 2018
  29. M. Andersson et al., “IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms,” EJNMMI Res. vol. 7, no. 88, Nov. 2017.
    DOI: 10.1186/s13550-017-0339-3
  30. Adult Reference Computational Phantoms, ICRP Publication 110, ICRP, Ottawa, Canada, 2009.
    DOI: 10.1016/j.icrp.2009.09.001
    PMid: 19897132