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Development of fast and sensitive methods for radiotoxicological and biodistribution studies/analyses of radionuclides used in medical applications (e.g. 225Ac)

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Targeted radionuclide therapy is a widely investigated approach for treatment of different types of cancers (Miederer et al., 2008; Elgqvist et al., 2014). Together with this approach, important challenges, such as “How to deal with recoiling daughters” (de Kruijff et al., 2015), “How the measure the biodistribution of radionuclides at sub-mm level” (Castillo Seoane et al., 2020), “How to detect multiple alpha sources” (Hooijman et al., 2021), need to be addressed as well.

With ongoing studies on radiolabelling and successive testing including in vivo and in vitro analysis of radionuclide concentrations and distributions also the radiation protection of the researchers and associated personnel needs to be considered. Radiotoxicological assay (e.g. in vitro analyses of excreta) for personnel professionally exposed, needs to be organized and methods needs to be developed/improved. These analyses methods for bio-assay can also be applied in studies to investigate organ specific radionuclide concentrations. After injection, (e.g. after 225Ac-chelates are injected) some ‘free’ fraction of the considered radionuclide (225Ac) and/or its recoil daughter products are free from the chelator and can accumulate in other organs than those targeted  (Davis et al. 1999; Hooijman et al., 2021).

To better understand the behavior of the short lived radionuclides and their decay products in the body, fast (in comparison to the half-lives of the radionuclides in the decay chain), sensitive and accurate measurements methods need to be developed. Sensitivity of the radioanalysis is generally obtained by applying chemical separation techniques to isolate specific radionuclides from the sample.

The work proposed in this project aims at answering the following research questions:

  1.  Are combined chemical separation and scintillation counting with PSm (Plastic scintillation microspheres) and PSresins (Plastic scintillation resins) selective and sensitive enough to be used for fast and accurate measurements of radionuclides considered in medical applications (225Ac and its daughter products) for radiotoxicological assay (low level activity) and studies of the activity distribution in different organs of test animals (medium to low-activity level).
  2.  The application of PSm and PSresins is to be compared with alpha-particle spectrometry for identification and quantification of 225Ac (and its daughter products) in different type of samples.

The aim of this study is to develop fast and sensitive methods for the quantification of alpha emitters and their decay products (225Ac) considered in medical applications. The methods will allow a fast estimation of an internal contamination of personnel working in production, radiolabeling and/or animal testing for the considered radionuclides. The same methods are applicable for the quantification of these radionuclides in biological matrices (internal organs, blood, urine) needed in biodistribution studies of radionuclides and/or their daughter products that are complementary or an addition to studies based on gamma-ray tomography e.g. SPECT.

References

Elgqvist J. et al., The potential and hurdles of targeted alpha therapy – clinical trials and beyond. Frontiers in oncology. 2014, vol 3, article 324.

I. A. Davis et al. Comparison of 225Ac chelates: Tissue distribution and Radiotoxicity. Nuclear Medicine & Biology. 1999, vol. 26, pp. 581–589.

R. Kruijff et al. A critical review of alpha radionuclide therapy – How to deal with recoiling daughters? Pharmaceuticals, 2015, vol. 8, 321-336.

Maxwell, S.L., Culligan, B.K., Hutchison, J.B., Utsey, R.C., McAlister, D.R., 2014. Rapid determination of actinides in seawater samples. J. Radioanal. Nucl. Chem. 300,

1175–1189. https://doi.org/10.1007/s10967-014-3079-0.

Tarancón, A.; Bagán, H.; García, J. F. Plastic scintillators and related analytical procedures for radionuclide analysis. Journal of Radioanalytical and Nuclear Chemistry. 314 - 2, pp. 555 - 572, (2017). DOI:10.1007/s10967-017-5494-5.

Tarancón, Alex; Bagán, Héctor.; García, José Francisco. Plastic Scintillators in Environmental Analysis. Chapter 13. p. 461-508 (2021). In book: Plastic Scintillators: Chemistry and Applications Editors: Hamel, Matthieu (Ed.) DOI:  10.1007/978-3-030-73488-6_13

The minimum diploma level of the candidate needs to be

  • Master of sciences

The candidate needs to have a background in

  • Chemistry
  • Radiochemistry

Estimated duration

4 years

Expert group

Low-level Radioactivity Measurements

SCK CEN Mentor

Vasile Mirela
mvasile [at] sckcen.be
+32 (0)14 33 28 31

Promotor

LEERMAKERS Martine
mleermak [at] vub.be

Co-promotor

Garcia Martinez Jose Francisco
jfgarcia [at] ub.edu