Quantifying 225Ac and its daughter radionuclides in biological samples

SCK•CEN Mentor

Vasile Mirela, mvasile@sckcen.be, +32 (0)14 33 28 31

Expert group

Low-level Radioactivity Measurements

SCK•CEN Co-mentor

De Saint-Hubert Marijke , mdsainth@sckcen.be , +32 (0)14 33 21 40

Introduction

The potential of Targeted α-particle Therapy (TAT) for treatment of different types of cancers has been widely acknowledged (Elgqvist J. et al., 2014). At SCK•CEN, the use of 225Ac (alpha-particle emitter) as one of the potential radionuclides to be applied in TAT, is being investigated. Once the labelled compound is injected to the patient, it targets a specific place where the tumor is present. Although 225Ac is one of the radionuclides which was used in clinical trials, the “toxicity is still an issue due to the recoil energy the daughters experience upon alpha decay” (Kruijff R., et al., 2015). Davis et al, compared different 225Ac chelators with respect to the tissue distribution and radiotoxicity (Davis I. A., 1999). They proved that 225Ac accumulates mainly in the liver and femur and to a lesser extend in the kidneys. However the organ accumulation is dependent on the types of chelating agents used to complex 225Ac. The toxicity effects studied by Davis et al., were attributed only to “free” 225Ac, and not to its redistributed daughter products since the distribution of the 221Fr is unknown (Davis I. A., 1999).

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. 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.

Objective

The aim of this thesis is to investigate if alpha-particle spectrometry together with gamma ray sprectrometry can determine and discriminate 225Ac and its daughter products in different types of matrices (liver, kidney blood and urine collected from mice). The focus will be to have a short turn-around time for sample preparation, to evaluate the interferences (matrix and spectral interferences) and to determine the appropriate tracers whenever a separation procedure is needed. The advantages, limitations and drawbacks given by both techniques, alpha-particle and gamma-ray spectrometry, will be summarized.

The minimum diploma level of the candidate needs to be

Academic bachelor , Professional bachelor

The candidate needs to have a background in

Chemistry