Department Seminar – Dr. Outi Keinänen, Research Fellow, Department of Chemistry, Hunter College (CUNY)
Apr 18, 2022
1:00PM to 2:00PM
Date(s) - 18/04/2022
1:00 pm - 2:00 pm
Title: Pretargeted PET imaging and radioimmunotherapy:Radiosynthesis inside a living body
Date: Monday, April 18, 2022
We are offering this seminar in hybrid format.
Room: ABB 163
Zoom: Please email email@example.com for Zoom details
Abstract: Over the past two decades,radiolabeled antibodies have become increasingly important tools for both thenuclear imaging and endoradiotherapy of cancer. Yet the long circulation timeof radioimmunoconjugates can lead to high radiation doses to healthy tissues.One approach to circumvent this limitation is in vivo pretargeting.Pretargeting relies upon performing radiosynthesis within the body. Theantibody is injected prior to the radionuclide, and the two components aredesigned to combine at the tumor itself. This approach shifts the radionuclidefrom the macromolecular immunoglobulin to a rapidly clearing small molecule,thereby facilitating the use of short-lived nuclides that are normallyincompatible with antibodies and reducing radiation dose rates to healthytissues. This talk focuses on a pretargeted system based on the rapid andbioorthogonal inverse electron-demand Diels-Alder (IEDDA) reaction between trans-cyclooctene(TCO) and tetrazine (Tz). This methodology has five elemental steps: (i) theadministration of the TCO-bearing immunoconjugate; (ii) an interval periodduring which the mAb-TCO slowly accumulates in the target tissue and clearsfrom the blood; (iii) the administration of the small molecule Tz radioligand;(iv) the in vivo click ligation between the two components; and (v) therapid clearance of any excess radioligand. This approach can produce highradioactivity concentrations in target tissues alongside reduced radiationdoses to healthy organs compared to traditional, directly radiolabeledimmunoconjugates.