Development and preclinical evaluation of 161Tb radiopharmaceuticals for cancer treatment

Cancer is one of the most frequently diagnosed diseases in the western world. Terbium has gather interest over the last decade as there are 4 radioisotopes which can be used in the medicinal space. Of these, 161Tb has become an interesting prospect for the radiopharmaceutical world, as it has both a therapeutic ß- decay (avg. energy = 0.15 MeV) and a diagnostic gamma (avg. energy = 49 keV). The therapeutic potential is greatly enhanced by the co-emission of Auger/conversion electrons (E = 36 keV), suitable for single cell irradiation. The overall objective of this PhD proposal is to develop and to pre-clinically evaluate a 161Tb-based radiopharmaceutical for the treatment of cancers. In this project, complexation chemistry of Terbium will be investigation and translated to radiochemical procedures for Terbium-161, these conditions will be optimised, in vitro and in vivo stability of 161Tb-labelled radiopharmaceuticals will be assessed, in vitro studies on tumour cell lines will be conducted, in vivo pharmacokinetics and therapeutic efficacy will be evaluated in relevant preclinical cancer mouse models and in vivo toxicity studies will be performed. This research project will be conducted by the Radiochemistry (RCY) group of the Belgian Nuclear Research Centre (SCK CEN) (under supervision of Dr Maarten Ooms and Dr Thomas Cardinaels) and the Laboratory of Radiopharmaceutical research (Ast Prof. Frederik Cleeren and Prof. Guy Bormans) and the Nuclear Medicine & Molecular Imaging group (Prof. Christophe Deroose) both of the University of Leuven (KU Leuven).