ESR8
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Alice D'Onofrio: ESR-8 Institute: IST Portugal Nationality: Italian |
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Working field: Synthesis, characterization and biological evaluation of Terbium-161 complexes as innovative tools for the imaging and treatment of ovarian cancer. The radiometal will be stabilized by a macrocyclic bifunctional chelator that will be conjugated to a tumor-specific MAb fragment and to Acridine Orange, a well-known DNA intercalator with high affinity for DNA, ensuring the proximity of 161Tb to the DNA in the nucleus of the tumor cells necessary for the therapeutic effect of short-range Auger electrons emitted by the radioisotope. Moreover, the conjugation of such bifunctional chelator to NIR probes is as well envisaged, in order to obtain bimodal probes with useful application for imaging. |
Post no.
ESR 8
Duration
36 months
Work package
WP3, D3.1: Design, synthesis and pre-clinical evaluation of multifunctional 161Tb complexes for cell specific targeting of DNA
Recruiting partner
Instituto Superior Técnico Lisbon, Portugal
Objective
161Terbium Auger-emitting radiopharmaceuticals for the eradication of large tumor masses or small metastases for ovarian cancers
Expected results
- Synthesis and characterization of macrocyclic bifunctional chelators (e.g. 1,4,7,10-tetraazacyclododecane DOTA) bearing a tumor-specific MAb fragment targeting moiety and a DNA-binding moiety).
- Synthesis of cold Tb complexes and characterization by spectroscopic techniques.
- Biological evaluation of Tb-161 complexes (Damage in plasmid DNA, Cell uptake using human tumor cell lines, Radiotoxicity and mechanisms of cell death, Biodistribution and SPECT imaging in tumor-bearing mice)
Enrolment for PhD at
Instituto Superior Técnico Lisbon, Portugal
Planned secondment(s)
CHUV, Switzerland – 2 months – μPET-SPECT imaging in nude mice
EPFL, Switzerland – 8 months – Synthesis of bifunctional fluorescent-Auger emitting bioligand targetting ovarian cancer DNA
