Assessment of exposure after injection of 99mTc-labeled intact monoclonal antibodies and their fragments into humans
Human pharmacokinetics and internal radiation dosimetry of normal organs after injection with the 99mTc-labeled monoclonal antibody (intact and fragments) are simulated by the WinAct program and IDAC (Internal Dose Assessment by Computer) software. The WinAct program is used to calculate the cumulative activity in organs and tissues. The calculated cumulative activity is inputted to the IDAC software, an internal dosimetry program for nuclear medicine based on the International Commission on Radiological Protection (ICRP) adult reference voxel phantom, and the absorbed doses by the organs and tissues are estimated. The obtained absorbed doses for the 99mTc-labeled monoclonal antibody (intact and fragments) are compared with the published figures by ICRP-128. The WinAct program method to calculate the cumulative activity is more accurate, as the fraction distribution, Fs, is described and calculated for organs, not only for intake, as in the ICRP model, but also for elimination.
KeywordsInternal exposure 99mTc Cumulative activity Monoclonal antibodies Absorbed dose
The work was partly supported by Act 211 of the Government of the Russian Federation (contract no 02. A03.21.0006) and the Centre of Excellence: Radiation and Nuclear Technologies.
Compliance with ethical standards
Conflict of interest
Mostafa Y.A. Mostafa has received research grants from Act 211 of the Government of the Russian Federation (contract no 02. A03.21.0006) and the Centre of Excellence: Radiation and Nuclear Technologies. Hesham M.H. Zakaly declares that he has no conflict of interest. Michael Zhukovsky declares that he has no conflict of interest.
This article does not contain any studies on human participants or animals.
Informed consent was obtained from all individual participants included in the study.
- 10.Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med. 1999;40:37S–61S.Google Scholar
- 11.Lindenberg M, Turkbey I, Adler S, Do K, Kummar S, Kurdziel K, et al. Dosimetry and first human experience with 89Zr panitumumab. J Nucl Med. 2015;56:1029-.Google Scholar
- 13.Fischman AJ, Khaw BA, Strauss HW. Quo vadis radioimmune imaging. J Nucl Med. 1989;30:1911–5.Google Scholar
- 14.Mattsson S, Johansson L, Leide Svegborn S, Liniecki J, NoÃƒÅ¸ke D, Riklund K, et al. ICRP publication 128: radiation dose to patients from radiopharmaceuticals: a compendium of current information related to frequently used substances. Ann ICRP. 2015;44:7–321. https://doi.org/10.1177/0146645314558019.CrossRefGoogle Scholar
- 16.Klibanov A, Martynov A, Slinkin M, Sakharov IY, Smirnov M, Muzykantov V, et al. Blood clearance of radiolabeled antibody: enhancement by lactosamination and treatment with biotin-avidin or anti-mouse IgG antibodies. J Nucl Med. 1988;29:1951–6.Google Scholar
- 17.Mould DR, Sweeney KRD. The pharmacokinetics and pharmacodynamics of monoclonal antibodies—mechanistic modeling applied to drug development. Curr Opin Drug Discov Dev. 2007;10:84–96.Google Scholar
- 18.Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers a H, Jager PL, de Jong JR, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87:586–92. https://doi.org/10.1038/clpt.2010.12.CrossRefGoogle Scholar
- 21.Oak Ridge National Laboratory, package of ORNL numerical solver (Windows version) for the coupled set of differential equations describing the kinetics of a radionuclide in the body WinAct v. 1.0, 2002. Retrieved from: https://www.ornl.gov/crpk/software
- 22.Andersson M, Johansson L, Eckerman K, Mattsson S. IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms. EJNMMI Res 2017;7. https://doi.org/10.1186/s13550-017-0339-3.