Internal Dosimetry assessment for monoclonal antibodies and antibody fragments labeled by Lutetium-177

H Mh Zakaly,M Y A Mostafa,M Zhukovsky

doi:10.1088/1742-6596/1353/1/012078

Abstract

In this research, the behaviour of monoclonal antibodies (MAbs) and their fragments labeled by 177Lu after injecting into the body is simulated for diagnostic and therapy. The absorbed doses in organs and tissues with maximum radiation exposure are presented. On the base of reference data in the literature, a biokinetic model is built-in for MAb and their fragments. The cumulative activity of 177Lu in organs and tissues per Bq of administered activity is calculated. Spleen, liver, and red bone marrow have the highest doses when 177Lu associated with intact monoclonal antibodies is injected into human body. The estimated doses on these organs are 1.95, 1.17 and 0.54 mGy/MBq, respectively. For the fragments of monoclonal antibodies is considered with 177Lu, the most exposed organs are the kidneys with the doses of 0.78 mGy/MBq for F(ab’)) and 1.27 mGy/MBq for F(ab′)2.

Highlights

One of the most promising drugs in the therapy of oncological diseases are considered to be short-lived βemitting radionuclides
A new generation of more realistic internal dosimetry models, including the Human Respiratory Tract Model [1] and recycling systemic models for actinides [2,3] had developed by ICRP
Conclusion x The biokinetic model is constructed for the dynamics of a radiopharmaceutical based on 177Lu, labeled with antibodies behavior in the body. x The dependences of the distributed activity in organs and tissues in time of its presence are presented, and the most irradiated organs are revealed. x For the most exposed organs, the dose coefficients on the unit of the injected activity were calculated. x It is shown that for the intact МАb administrated 177Lu in the body the most exposed organs are the spleen, liver, kidneys and red marrow when administered 177Lu bound to fragments of MAb F(ab)c2 – the kidneys, spleen, liver and red marrow

Summary

Introduction

One of the most promising drugs in the therapy of oncological diseases are considered to be short-lived βemitting radionuclides. Such nuclides apply 177Lu. 177Lu is a beta radiating nuclide with the energy of 0.49 MeV and a half-life of 6.7 days (161 h). This allows scintigraphy in the process of therapy. The 3rd European Intercomparison Exercise on Internal Dose Assessment carried out in the framework of EULEP/EURADOS/UIR concerted action “Environmental and occupational dosimetry: an integrated approach to radiation protection covering radioecology, dosimetry, and biological effects" provided special insight into the effects of the new models and the choice of input parameters on the assessment of internal doses from monitoring results [4]

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Results

Conclusion