Vejleder: Christine McKenzie og medvejleder(e): Dr. Ellis Smith og/eller Mads Sondrup Møller
Projektbeskrivelse
We aim to invent enabling technology for implementing radioactive antimony and cobalt isotopes (119Sb or 58mCo) with decay properties superior to those used currently in the clinic for radiopharmaceutical cancer therapy. As Auger electron emitters with a cell-sized, short range of radioactive decay, new radiopharmaceuticals based on these radioisotopes are predicted to minimize damage to surrounding healthy tissue. Incredibly fortuitously, sister isotopes 117Sb or 55Co will allow monitoring of treatment progress using PET/SPECT-CT scanners. Although the radioactivity of the different isotopes of the same element is different, the chemistry is the same. This means that the same transporter molecules - which we will invent - can be used for different isotopes of the same element.
We have previously documented that the chelators most commonly used in the clinic as vectors for transporting radioactive metal ions to cancer tumors, e.g., “DOTA” cannot be used for Sb.[1] We are therefore designing and synthesizing entirely new biocompatible transporter molecules for the unprecedented administration of 119/117Sb to patients.
Work involves synthesis, spectroscopy, and X-ray diffraction in characterising “cold” Sb and Co complexes. The “hot” counterparts of promising candidate will then be prepared at Odense University Hospital (OUH) and tested for selective uptake into cancer cell lines. Really promising systems are then tested in human tumor xenographt mice models (Figure 1).
We always watch out for serendipitous discoveries, and a bonus of this work is that the chemistry of Sb is particularly underdeveloped. We may discover a compound with unexpected application to an entirely different field, e.g., catalysis.
This work is a collaboration with Assoc. Prof. Helge Thisgaard[1] of the Nuclear Medicine department at OUH and funded by the NovoNordisk Foundation.
[1] H. Thisgaard, et al., Highly Effective Auger-Electron Therapy in an Orthotopic Glioblastoma Xenograft Model using Convection-Enhanced Delivery. Theranostics, 2016. 6, 2278-2291; J. H. Dam, et al., A PSMA Ligand Labelled with Cobalt-55 for PET Imaging of Prostate Cancer. Mol Imaging Biol, 2017, 19, 915-922.
[2] C. Chen, C. Sommer, H. Thisgaard, V. McKee and C. J. McKenzie, Facile Transmetallation of [SbIII(DOTA)]- Renders it Unsuitable for Medical Applications, RSC Advances, 2022, 12, 5772-5781.