PhD Defense | Clarita Saldarriaga Vargas | Radiation dosimetry to support the preclinical investigation and further development of radiopharmaceutical therapy

Radiation dosimetry to support the preclinical investigation and further development of radiopharmaceutical therapy

Research studies on laboratory animals are essential to understand the underlying mechanisms of cancer and to investigate how to treat cancer safely and effectively. Preclinical animal studies are also required by regulators before new drugs, including radiopharmaceuticals, can be evaluated in humans. More specifically, knowledge on the radiobiological and biophysical basis of tissue response upon irradiations with radiopharmaceuticals may be best obtained in in vivo models, where a controlled and systematic study of the radiopharmaceutical and radiation dose distribution, and diverse biological endpoints of tissue response is possible. This kind of quantitative investigations require appropriate methods which allow a meaningful and reliable assessment of the quantities used for analyzing radiobiological outcomes. This will improve the correlations between input and output variables (e.g., toxicity versus absorbed dose) upon which sound conclusions with an increased translatability to humans can be formulated.

The developments addressed in this PhD relate to the accuracy evaluation or improvement of methods used (i) for activity quantification of radiopharmaceuticals prior to administration in humans or laboratory animals, (ii) for radiopharmaceutical activity quantification in tissues of laboratory mice, and (iii) for radiation absorbed dose estimations of radiopharmaceuticals in mouse kidney tissues. This PhD thesis shows how these topics are important for using radiation dosimetry and dose–response modelling as tools for evaluating the safety of novel radiopharmaceuticals during the preclinical development phase and/or for individualized treatment optimization in clinical applications.

Promotor:

• Peter Covens (VUB)

Co-Promotor:

• Vicky Caveliers (VUB)

SCK CEN mentors:

• Lara Struelens (SCK CEN)

Click here for a list of obtained PhD degrees.