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Genotoxic hazard of radiopharmaceuticals in humans: chemical and radiation aspects coupled to microdosing

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Abstract

Introduction

To obtain the pharmacokinetic properties of drug candidates at an early stage of the development process, a microdosing (phase 0) concept to radiolabel drug candidates and administer them at subtoxic mass to a few volunteers has been suggested. Radiopharmaceuticals are special in the sense that the chemical carrier might be genotoxic, whereas it is well established that ionizing radiation coupled to the molecule is genotoxic, and that the mechanism that causes cancer is similar to certain genotoxic chemicals.

Regulatory perspectives of the levels of toxicity

An analysis shows that, e.g., positron emission tomography (PET) pharmaceuticals carry a mass less than what is regarded as an acceptable level of a genotoxic impurity. It has also been shown that the estimated genotoxicity hazard of the radioactivity is 10–100 times higher than that of the administered chemicals.

Conclusion

As radiation doses at this level are accepted in clinical trials, the conclusion is that the regulatory demands on radiopharmaceuticals produced at high specific radioactivity should be reconsidered in order to facilitate the use of the microdosing concept for drug development.

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Authors and Affiliations

  1. Biomedical Radiation Sciences, Uppsala University, 751 85, Uppsala, Sweden

    H. Lundqvist

  2. Uppsala Imanet AB, Uppsala, Sweden

    G. Antoni

  3. Department of Biochemistry and Organic Chemistry, Uppsala University, Box 567, 75109, Uppsala, Sweden

    B. Långström

Authors
  1. H. Lundqvist
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  2. G. Antoni
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  3. B. Långström
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Correspondence to H. Lundqvist.

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Lundqvist, H., Antoni, G. & Långström, B. Genotoxic hazard of radiopharmaceuticals in humans: chemical and radiation aspects coupled to microdosing. Eur J Clin Pharmacol 63, 641–645 (2007). https://doi.org/10.1007/s00228-007-0304-6

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  • DOI: https://doi.org/10.1007/s00228-007-0304-6

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