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Genotoxic hazard of radiopharmaceuticals in humans: chemical and radiation aspects coupled to microdosing
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
2007 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 63, no 7, 641-645 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2007. Vol. 63, no 7, 641-645 p.
Keyword [en]
Genotoxicity, Radiopharmaceuticals, Microdosing
National Category
Chemical Sciences Medical and Health Sciences Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-14996DOI: 10.1007/s00228-007-0304-6ISI: 000247238600002OAI: oai:DiVA.org:uu-14996DiVA: diva2:42767
Available from: 2008-02-01 Created: 2008-02-01 Last updated: 2015-09-24Bibliographically approved

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Antoni, GunnarLångström, Bengt
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Biomedical Radiation SciencesDepartment of Biochemistry and Organic Chemistry
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