Targeted radionuclide therapy: how to correlate microdosimetry with biological effects
Targeted radionuclide therapy (TRT) can be a potent therapy modality for treatment of systemic malignancies. In TRT, a radioactive isotope is attached to a biological vector, forming a radiopharmaceutical that selectively seeks out tumor cells. Hence, in contrast to external beam radiotherapy (EBRT), TRT offers the advantage to attack multiple sites throughout the body.
Despite the clinical success of TRT, its value can be increased by tailoring the treatment to the patient-specific needs. In this respect, radiation dose calculations, i.e. dosimetry, form a valuable instrument to optimize TRT with individualized regimens to reduce toxicity and increase tumor responses. Moreover, radiobiology for TRT still follows the traditional pathways set out by the pioneering work in EBRT, despite evidence suggesting that cellular and molecular mechanisms characterizing cellular response to low dose and/or prolonged low dose rate radiation exposures (i.e., TRT) can be quite different from those occurring at high dose rate (i.e., EBRT). Modelling and understanding these mechanisms on a preclinical level is of uttermost importance to guide translational and clinical advances.
Therefore, the aim of this work is to improve the current computational dosimetry approaches for in vitro and in vivo TRT treatment in order to correlate microdosimetry with biological effects. The creation of such computational frameworks and the investigation of the radiobiology of dose-response in TRT in cells and in small animals can ultimately lead to a better understanding of this treatment modality and to increase the predictive power of dosimetry.
F.A. Verburg (EU Rotterdam)
- M.W. Konijnenberg (EU Rotterdam)
- J. Nonnekens (EU Rotterdam)
SCK CEN mentors:
Marijke de Saint-Hubert (SCK CEN)
Lara Struelens (SCK CEN)
Click here for a list of obtained PhD degrees.