Date of Degree
Brian M. Zeglis
Jason S. Lewis
Lynn C. Francesconi
Rein V. Ulijn
Kevin H. Gardner
Pretargeting, Radiochemistry, peptide amphiphile
The role of antibody-based imaging of cancer by positron emission tomography (PET) has expanded significantly in recent years and is poised to radically alter the way that cancer is diagnosed and treated. However, one hurdle that remains is the potentially harmful radiation dose that comes from these imaging agents, as the long circulation time of antibodies (days to weeks) necessitates the use of radionuclides with comparable physical half-lives (i.e. 89Zr, 124I, etc.). One particularly promising solution is the use of the inverse electron demand Diels-Alder (IEDDA) reaction between a 1,2,4,5-tetrazine (Tz) and a trans-cyclooctene (TCO) for pretargeting. By separately injecting antibody and radioligand and allowing the two to “click” in vivo, overall dose to the patient can be reduced nearly 45-fold. The first half of the dissertation to follow seeks to optimize both antibody and radioligand, while setting the stage for eventual clinical translation. The second half explores the emergence of enzyme-responsive nanomaterials in an attempt to develop a PET imaging agent for MMP-9 activity.
Cook, Brendon E., "The Development of Novel Platforms for the Imaging of Cancer by Positron Emission Tomography" (2018). CUNY Academic Works.