PhD vacancy - Prediction of Ac-225 dose–response based on Lu-177 pharmacokinetics

Position: PhD vacancy (4 y, starting in October 2024)

Institution: Belgian Nuclear Research Centre (SCK CEN)

Location: Mol, Belgium

Application closes at: Mar 20th, 2024 23:00

URL: https://www.sckcen.be/en/PhD_MNA_TRA_Prediction_of_dose

PhD vacancy - Prediction of Ac-225 dose–response based on Lu-177 pharmacokinetics

In radiopharmaceutical therapy patient dosimetry requires activity quantification over time through imaging. For the beta emitter 177Lu this is being established with quantitative SPECT imaging. For the alpha emitter 225Ac, however, this is challenging because of the low abundancy of gamma rays and low administered activities, which currently precludes treatment concomitant dosimetry. Complementary approaches for determining 225Ac pharmacokinetics in tissues are therefore needed.

The PhD project aims to investigate and compare the pharmacokinetic, dosimetric and radiobiological behavior of 225Ac- and 177Lu-ligands in preclinical settings, both on cells and on mice. The PhD will investigate whether the pharmacokinetics of 177Lu can be used to predict the pharmacokinetics of 225Ac, by considering (i) the potential recoiling daughter effect of 225Ac daughters and (ii) the microscopic distribution of radioligand within tissues. Additionally, the PhD will revisit the relative biological effectiveness (RBE) of 225Ac- vs 177Lu-ligands for relevant organs at risk to better predict differences in radiotoxic effects between both therapies.

As a result, the PhD will provide ground knowledge for increasing the clinical application of image-guided dosimetry during 177Lu- and 225Ac-therapy such that therapeutic doses can be tailored for each patient individually to achieve a better risk-benefit balance and improved efficacy.

The PhD will be part of a larger European project (LutaDose) with a consortium composed out of preclinical and clinical centers.

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