BRIC Seminar Series December 2016

Join us for a presentation by Dr. Michael Zalutsky, Jonathan Spicehandler Professor of Neuro-Oncology Research, Duke.

When Dec 07, 2016
from 12:00 PM to 01:00 PM
Where Marsico 4004
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Michael Zalutsky 12_07_2016

Join us on December 7th, 2016 at 12:00 PM in Marsico Hall, room 4004, for a presentation of "Single Domain VHH and Other Molecules for Targeted Radiotherapy and Molecular Imaging of Cancer" by Dr. Michael Zalutsky, Ph.D. of Duke University. 

Abstract:

Camels and llamas are distinctive not only because of their appearance but because they produce heavy-chain only antibodies that are characterized by single chain variable domains.  These VHH molecules (also known as nanobodies) have a molecular weight of ~15 kDa, an order of magnitude smaller than immunoglobulins and are the smallest function fragment of a naturally occurring antibody.  Unlike intact antibodies, which are an order of magnitude larger, VHH have a pharmacokinetic profile that is well matched to the short physical half lives of many of the most promising radionuclides for SPECT and PET imaging as well as targeted radiotherapy. VHH have been generated with 1-5 nM affinity for multiple molecular targets of potential interest as imaging tools for oncology, cardiology and immunology.  The focus of our current work has been the development and evaluation of methodologies for labeling anti-HER2 VHH for receptor targeted imaging and molecular radiotherapy.  Our results show the importance of utilizing a labeled prosthetic group that become trapped in target cells after receptor mediated internalization of the VHH.  With optimal approaches, uptake of radioactivity in human tumor xenografts in murine models approach’s that typically obtained with whole immunoglobulins but will significantly reduced normal tissue levels, improving image contrast and reducing normal tissue dose.  If similar results should be attainable with other VHH, the methods which have been developed for labeling these molecules with 18F, 124/131/123I and 211At might serve as a valuable toolbox for advancing molecular imaging and targeted radiotherapy with this promising protein scaffold.