The Development of Novel Platforms for the Imaging of Cancer by Positron Emission Tomography

<p>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 <em>trans</em>-cyclooctene (TCO) for pretargeting. By separately injecting antibody and radioligand and allowing the two to “click” <em>in vivo</em>, 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.</p>

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor

The Graduate School and University Center of The City University of New York

Year dc:date.available

2018

Author dc:creator

• Cook, Brendon E

Advisor dc:contributor.advisor

• Brian M. Zeglis

Committee members dc:contributor.committeemember

• Jason S. Lewis
• Lynn C. Francesconi
• Rein V. Ulijn
• Kevin H. Gardner

• Radiochemistry
• Pretargeting
• peptide amphiphile

Repository record dc:identifier

https://academicworks.cuny.edu/gc_etds/2783

OAI identifier oai:identifier

oai:academicworks.cuny.edu:gc_etds-3845