Join Dr. Elaheh Khozeimeh Sarbisheh – SHRF and CIHR postdoctoral research fellow, University of Saskatchewan for the lecture titled “Next-Generation of Radiometal Chelators with Enhanced Stability“
All welcome. Light refreshments will be provided.
Next-Generation of Radiometal Chelators with Enhanced Stability
Positron Emission Tomography (PET) imaging is a critical tool for early diagnosis of cancer and improving patients’ survival rate. Zirconium-89 features a half-life matched to antibody biovectors (78.4 hours), favorable decay characteristics for PET imaging, and routine production at a growing number of cyclotron sites world-wide. However, successful use of zirconium-89 requires stable radiometal-bifunctional chelator (BFC) complexes for effective tethering to biovectors. To avoid chelate-instability and leaching of free zirconium-89 into the patient’s body, a BFC with eight oxo-coordination sites to Zr(IV) is ideal. Since the gold-standard chelator for zirconium-89 — desferrioxamine (DFO) — provides a sub-optimal six oxo-coordination sphere, new BFCs with eight oxo-donor sites have been sought after by many research groups in recent years. Although a few successful new BFCs for zirconium-89 have been published in recent years, we are designing new BFCs and more importantly investigating the use of EXAFS spectroscopy and DFT computational methods towards the elucidation of the possible coordination spheres of our metal-chelate complexes. A series of new high-denticity (CN=12) chelators have been synthesized and the complexation of these new chelators with non-radioactive metal ions including Zr(IV) and Ti(IV) are being investigated via DFT and EXAFS. Preliminary zirconium-89 radiolabeling and stability assays have demonstrated that zirconium-89 complexes of DFO2 and several of its derivatives are more stable than DFO. Synthesis of bifunctional derivatives of DFO2-type chelators are ongoing to facilitate antibody conjugation and in vivo stability evaluation, where we hope to find a predictive link between our spectroscopic and computational studies and in vivo performance.